Beta 1-selectivity of bisoprolol, a new beta-adrenoceptor antagonist, in anesthetized dogs and guinea pigs.
The beta-adrenoceptor activity of the newly synthesized antagonist bisoprolol [+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol, hemifumarate), has been compared with the effect of several reference compounds in anesthetized dogs and guinea pigs. In anesthetized, bivagotomized dogs, isoprenaline dose-response relations for increase in heart rate and decrease in diastolic blood pressure were established. Bisoprolol had the largest beta 1/beta 2 ratio, i.e., 147 (102-292). Practolol showed a beta 1/beta 2 ratio greater than 17; betaxolol 6-15; acebutolol, atenolol, and metoprolol 1.1-3.2; mepindolol 0.6-1 and propranolol 0.2. In artificially ventilated guinea pigs, the activity of bisoprolol on histamine-induced increase in tracheal lateral pressure (TLP) and basal heart rate (HR) was tested: using doses taken at TLP (30 mm Hg) and HR (250 beats/min), bisoprolol exhibited the most pronounced ratio TLP/HR of 124 +/- 59, followed by atenolol 33 +/- 23, metoprolol 25 +/- 15, betaxolol 12 +/- 4, propranolol 1 +/- 0.3, and celiprolol 0.23 +/- 0.19. These experiments indicate that bisoprolol possesses a pronounced beta 1-selectivity, which seems to be superior to that of known beta 1-selective antagonists.


The yeast cell cortical protein Num1 integrates mitochondrial dynamics into cellular architecture.
During the cell cycle each organelle has to be faithfully partitioned to the daughter cells. However, the mechanisms controlling organellar inheritance remain poorly understood. We studied the contribution of the cell cortex protein, Num1, to mitochondrial partitioning in yeast. Live-cell microscopy revealed that Num1 is required for attachment of mitochondria to the cell cortex and retention in mother cells. Electron tomography of anchoring sites revealed plasma membrane invaginations directly contacting the mitochondrial outer membrane. Expression of chimeric plasma membrane tethers rescued mitochondrial fission defects in Δnum1 and Δmdm36 mutants. These findings provide new insights into the coupling of mitochondrial dynamics, immobilization, and retention during inheritance.


[Creation and functioning of Covid-19 pre-hospital triage centres : experience of french-speaking GP-coordinators].
Pre-hospital triage centres were created during the first wave of Covid-19 in March 2020. The intention was to examine patients in appropriate sanitary conditions and prevent emergency departments from overcrowding. This study describes triage centres in the Federation Wallonia-Brussels. The aim of the study was to collect key aspects of triage centres, implementation and information about the daily functioning interpreted positively or negatively by the GP-coordinators in charge of their management. This study was divided into two parts : an online questionnaire and semi-structured interviews. Overall, 14 questionnaires and 6 interviews were collected among the 44 initially contacted GP-coordinators. Our results point to a highly heterogeneous organisation of the triage centres, nevertheless adapted to local contexts, as well as a gap between local effective dynamics and challenges regarding federal/regional cooperation. This study may help for further crisis management plans.


Cell damage by cytolysin. Spontaneous recovery and reversible inhibition by divalent cations.
Cytolysin-induced membrane damage (which requires low Ca2+) has been studied 1) in E by assay of hemolysis, 2) in Lettre cells by measurement of transmembrane potential, intracellular content of K+ and Na+, leakage of phosphoryl[3H]choline or 51Cr from [3H]choline-labeled or 51CrO4(2-)-labeled cells and leakage of lactate dehydrogenase, and 3) in phospholipid bilayers by measurement of electrical conductivity changes. In Lettre cells, damage is restricted and reversible: little lactate dehydrogenase leaks from cells that leak substantial amounts of Na+, K+, and phosphoryl[3H]choline; at low amounts of cytolysin, membrane potential and intracellular content of Na+ and K+ recover within minutes. In E and Lettre cells, membrane damage is inhibited by Zn2+, by high Ca2+, or by low pH. Inhibition is reversible: addition of EGTA to Zn2+-protected E or Lettre cells (incubated in the presence of cytolysin, low Ca2+ and Zn2+) initiates leakage; removal of Zn2+ (and cytolysin and Ca2+) by washing also initiates leakage; such leakage is again sensitive to Zn2+, high Ca2+, or H+. In phospholipid bilayers, channels induced by cytolysin (at low Ca2+) are partially closed by negative voltage; Ca2+, Zn2+, or H+ promote channel closure. Channels are re-opened (only partially in the case of Zn2+) by positive voltage. From all these results it is concluded that the action of cytolysin on membranes is similar to that of other pore-forming agents: damage does not necessarily lead to lysis of nucleated cells, and can be prevented by Ca2+, Zn2+, or H+.


Interleukin-33: a mediator of inflammation targeting hematopoietic stem and progenitor cells and their progenies.
Inflammation is defined as a physiological response initiated by a variety of conditions that cause insult to the body, such as infection and tissue injury. Inflammation is triggered by specialized receptors in the innate immune system, which recognize microbial components known as pathogen-associated molecular patterns or endogenous signals produced by damaged cells (damage-associated molecular patterns). IL-33 is a cytokine that is released predominantly at the epithelial barrier when it is exposed to pathogens, allergens, or injury-inducing stimuli. IL-33 target cells are various, ranging from hematopoietic stem and progenitor cells (HSPCs) and essentially all types of their progeny to many non-hematopoietic cells. The pleiotropic actions of IL-33 suggest that IL-33 is involved in every phase of the inflammatory process. In this review, we discuss recent advances in the understanding of how IL-33 orchestrates inflammatory responses by regulating HSPCs and innate immune cells.


Crystallization and preliminary crystallographic investigations of the soluble glucose dehydrogenase from Acinetobacter calcoaceticus.
Single crystals of the soluble glucose dehydrogenase (GDH) from Acinetobacter calcoaceticus have been grown by the vapour diffusion method. These crystals diffract to beyond 2.1 A and are suitable for X-ray crystallography. The space group was determined to be P2(1) with unit cell parameters a = 55.5 A, b = 104.5 A, c = 86.5 A and beta = 99.8 degrees. One asymmetric unit contains a dimer of the GDH molecule.


Management of war-related burn injuries: lessons learned from recent ongoing conflicts providing exceptional care in unusual places.
Thermal injury is a sad but common and obligatory component of armed conflicts. Although the frequency of noncombat burns has decreased, overall incidence of burns in current military operations has nearly doubled during the past few years. Burn injuries in the military environment do not need to be hostile in nature. Burns resulting from carelessness outnumber those resulting from hostile action. Unfortunately, civilians are becoming the major targets in modern-day conflicts; they account for more than 80% of those killed and wounded in present-day conflicts. The provision of military burn care mirrors the civilian standards; however, several aspects of treatment of war-related burn injuries are peculiar to the war situation itself and to the specific conditions of each armed conflict. Important aspects of management of burned military personnel include triage to ensure that available medical care resources are matched to the severity of burn injury and the number of burn casualties, initial management and resuscitation in the combat zone, and subsequent evacuation to higher echelons of medical care, each with increasing medical capabilities. Care of military victims is usually well structured and follows strict guidelines for first aid and evacuation to field hospitals by military personnel usually having had some form of training in first aid and resuscitation and for which necessary equipment and material for such interventions are more or less available. Options available for civilian injury intervention in wartime, however, are limited. Of all pre-hospital transport of civilian victims, 70% are done by lay public and 93% receive in the field, or during transport, some form of basic first aid administered by relatives, friends, or other first responders not trained for such interventions. Civilian casualties frequently represents 60% to 80% of all injured admitted to the level III facilities of overseas forces stationed throughout the host country. Unlike military personnel who are rapidly evacuated to higher echelons IV and V for definitive and long-term care, civilians must receive definitive burn treatment at these level III military facilities. The present review was intended to highlight peculiar aspects of war-related burn injuries of both military personnel and civilians and their management based on the most recently published material that, for the most part, is related to the recent conflicts in Iraq and Afghanistan.


Supraclavicular artery flap: a new option for pharyngeal reconstruction.
Laryngopharyngeal oncologic resections produce complex reconstructive problems, requiring dependable robust flaps to restore form and function. Current options include morbid local-regional flaps or free tissue transfers. The supraclavicular artery flap (SAF) offers a great new option. Partial pharyngeal oncologic defects were reconstructed with pedicled SAFs. Handheld Doppler probes marked the pedicle preoperatively. Flaps were design based upon the dopplered vascular anatomy. Complications and functional outcomes were assessed. All flaps (n = 6) were harvested in under 1 hour with uneventful postoperative recoveries. Ablative wounds and donor sites were closed primarily. Two patients had small controlled leaks because of preoperative radiation and overly aggressive oral intakes, that subsequently resolved. There were no functional donor site morbidities. We describe a novel application of the SAF for pharyngeal reconstructions after laryngopharyngeal cancer ablation. This thin, reliable, easy to harvest, low morbidity flap is an excellent reconstructive option for pharyngeal reconstructions.


Expression of the basement membrane heparan sulfate proteoglycan (perlecan) in human synovium and in cultured human synovial cells.
Perlecan is a heparan sulfate proteoglycan that has a core protein of 466 kDa and is composed of five modules, four of which share a high degree of homology with a variety of biologically important molecules including the low-density lipoprotein receptor, laminin, and the neural cell adhesion molecule. Previously, this specialized proteoglycan, characteristic of the basement membrane, was not identified as a constitutive extracellular component of human synovium. Using human synovium and cultured human synovial cells, we examined perlecan gene expression in human synovium, a tissue lacking a classic basement membrane. The modulation of gene expression of the perlecan core protein by transforming growth factor-beta (TGF-beta) and basic fibroblast growth factor (FGF) was examined in cultures of normal human synovial cells, and by metabolic labeling using radioactive sodium sulfate, the question of whether this specialized protein is produced by synovial cells as a proteoglycan was addressed. Cultures of normal human synovial cells were shown to contain the large 14.5 kb perlecan mRNA and produced substantial amounts of perlecan core protein as shown by immunohistochemistry employing specific human perlecan Ab. Immunohistochemical detection showed intense staining in the intimal and subintimal layers of human synovial membrane. Moreover, the perlecan core protein was shown to be up-regulated by TGF-beta and down-regulated by basic FGF. In addition, a sizable portion (approximately 25%) of the synovial cell-produced proteoglycan was shown to contain heparan sulfate, providing evidence that synovial cell perlecan is produced as a proteoglycan. The presence of perlecan in human synovium and the modulation of the biosynthesis of its core protein by TGF-beta and FGF suggest that, in addition to its structural role, this unique heparan sulfate proteoglycan may be involved in normal synovial membrane function and in the pathogenesis of arthritis.


Pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol following a single induction dose administered intravenously in cats.
To compare the pharmacokinetics and pharmacodynamics of propofol with or without 2% benzyl alcohol administered intravenously (IV) as a single induction dose in cats. Prospective experimental study. Six healthy adult cats, three female intact, three male castrated, weighing 4.8 ± 1.8 kg. Cats received 8 mg kg(-1) IV of propofol (P) or propofol with 2% benzyl alcohol (P28) using a randomized crossover design. Venous blood samples were collected at predetermined time points to 24 hours after drug administration to determine drug plasma concentrations. Physiologic and behavioral variables were also recorded. Propofol and benzyl alcohol concentrations were determined using high pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were described using a 2-compartment model. Pharmacokinetic and pharmacodynamic parameters were analyzed using repeated measures anova (p < 0.05). Plasma concentrations of benzyl alcohol were below the lower limits of quantification (LLOQ) at all time points for two of the six cats (33%), and by 30 minutes for the remaining four cats. Propofol pharmacokinetics, with or without 2% benzyl alcohol, were characterized by rapid distribution, a long elimination phase, and a large volume of distribution. No differences were noted between treatments with the exception of clearance from the second compartment (CLD2), which was 23.6 and 38.8 mL kg(-1) minute(-1) in the P and P28 treatments, respectively. Physiologic and behavioral variables were not different between treatments with the exception of heart rate at 4 hours post administration. The addition of 2% benzyl alcohol as a preservative minimally altered the pharmacokinetics and pharmacodynamics of propofol 1% emulsion when administered as a single IV bolus in this group of cats. These data support the cautious use of propofol with 2% benzyl alcohol for induction of anesthesia in healthy cats.


Affordable Thin Lens Using Single Polarized Disparate Filter Arrays for Beyond 5G toward 6G.
This paper proposes a novel design approach for a thin lens with the aim of overcoming fineness limits in the commercial millimeter wave printed circuit board (PCB) manufacturing process. The PCB manufacturing process typically does not allow the fabrication of metallic patterns with a gap and width of less than 100 μm. This hampers expanding thin lens technology to 5G commercial applications, especially when such technology is considered for 60 GHz or higher frequency, which requires a finer gap and width of metallic traces. This paper proposes that problematic process conditions can be mitigated when a lens is designed by establishing single-polarized lumped element models where larger capacitance and inductance values can be obtained for the same patch and grid unit cells. While the proposed design technique is more advantageous at higher target frequencies, a 60 GHz application and a wireless backhaul system is selected because of a limited range of frequencies that can be measured by an available vector network analyzer. The required gap or width of metallic traces can be widened significantly by using the proposed single-polarized unit cells to acquire the same in-plane capacitance or inductance. This enables the lens operating at higher-frequency under the process limits in fabricable fine traces. Finally, the effectiveness of the simulated design procedure is demonstrated by fabricating a 60 GHz thin lens that can achieve a gain enhancement of 16 dB for a 4 × 4 patch antenna array with a gain of 16.5 dBi.


Medicine as a career among 1974 and 1977 British medical qualifiers.
Information was obtained for about 95% of 1974 and 1977 qualifiers from British/UK medical schools. The percentages giving medicine as a career choice were much lower some years after qualifying than in the pre-registration year. A third of those working in medicine 13 years after qualifying were consultants, but 9 years after qualifying almost 90% of those who had initially given medicine as a first career choice had not become senior registrars or consultants in a medical discipline. Just over 6% of respondents had obtained medical experience abroad at some stage. Only 10 consultants in medical disciplines described having worked in general practice. Among 1974 qualifiers who had been medical registrars, 34% were medical consultants, 6% were consultants in non-medical specialties and 20% were general practitioners, when surveyed 13 years after qualifying. Details are given of individual medical specialties.


Identification, Characterization and Synthesis of Walterospermin, a Sperm Motility Activator from the Egyptian Black Snake Walterinnesia aegyptia Venom.
Animal venoms are small natural mixtures highly enriched in bioactive components. They are known to target at least two important pharmacological classes of cell surface receptors: ion channels and G protein coupled receptors. Since sperm cells express a wide variety of ion channels and membrane receptors, required for the control of cell motility and acrosome reaction, two functions that are defective in infertility issues, animal venoms should contain interesting compounds capable of modulating these two essential physiological functions. Herein, we screened for bioactive compounds from the venom of the Egyptian black snake Walterinnesia aegyptia (Wa) that possess the property to activate sperm motility in vitro from male mice OF1. Using RP-HPLC and cation exchange chromatography, we identified a new toxin of 6389.89 Da (termed walterospermin) that activates sperm motility. Walterospermin was de novo sequenced using a combination of matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF MS/MS) and liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF MS/MS) following reduction, alkylation, and enzymatic proteolytic digestion with trypsin, chymotrypsin or V8 protease. The peptide is 57 amino acid residues long and contains three disulfide bridges and was found to be identical to the previously cloned Wa Kunitz-type protease inhibitor II (Wa Kln-II) sequence. Moreover, it has strong homology with several other hitherto cloned Elapidae and Viperidae snake toxins suggesting that it belongs to a family of compounds able to regulate sperm function. The synthetic peptide shows promising activation of sperm motility from a variety of species, including humans. Its fluorescently-labelled analog predominantly marks the flagellum, a localization in agreement with a receptor that controls motility function.


Vitamin D and L-Isoleucine Promote Antimicrobial Peptide hBD-2 Production in Peripheral Blood Mononuclear Cells from Elderly Individuals.
Elderly individuals are susceptible to develop infectious diseases; promoting innate immunity to prevent infections is a key issue. Human β-defensin-2 (hBD-2) is an antimicrobial peptide with antimicrobial and immunomodulatory properties. L-isoleucine and vitamin D are important molecules that induce hBD-2. The Aim of this study was to determine the use L-isoleucine and Vitamin D to induce hBD-2 in cells from healthy elderly individuals and elderly individuals with recurrent infections. We explored three groups: young adults (n = 20) used as control group, elderly adults (n = 18) and elderly with recurrent infections (n = 11). PBMCs (peripheral blood mononuclear cells) were isolated from the different groups and then were treated with L-isoleucine or vitamin D3. hBD-2 concentration was assessed with a sandwich enzyme Immunosorbent assay by triplicate. Using the vehicle as a mock control. Our results showed that a percentage of the individuals responded to the treatments producing hBD-2 (p < 0.05). These results showed that both molecules induced hBD-2 in elderly individuals and can be potentially used as prophylactic therapy to decrease infection diseases rates in this vulnerable group.


Unusual location of eosinophilic granuloma.
Eosinophilic granuloma EG is a benign self-limiting disease, which belongs to the spectrum of Langerhans' cell histiocytosis LCH. The etiology of LCH remains unknown, although the evidence indicates that it is a clonal proliferative disorder of Langerhans cells, it has also been characterized as reactive disorder, neoplastic process and a berrant immune response. Eosinophilic granuloma is characterized by single or multiple skeletal lesions occurring predominately in children, adolescents and young adults, it accounts for 70% of LCH. It is more common in males, and the common sites are the skull, mandible, ribs, spines and long bones particularly the femur and the humerus. The estimated incidence of EG is 3-4 per million of the population. Vertebral bone involvement is rarely seen and usually affects the vertebral body. We are reporting an unusual case of EG in a female child presented with a solitary lesion at posterior element of lumbar vertebra.


Redundant surgical publications: tip of the iceberg?
A redundant publication is one which duplicates previous, simultaneous, or future publications by the same author or group or, alternatively, could have been combined with the latter into one paper. As there is no information about the extent of this problem in the surgical literature, we set out to assess the incidence, spectrum, and salient characteristics of redundant publications in 3 leading surgical journals. Original articles (excluding reviews, editorials, abstracts, and letters) published during 1998 in the journals Surgery, The British Journal of Surgery, and Archives of Surgery were searched by using the on-line search engine PUBMED. Each original article was scrutinized to identify redundancy by combining the names of the first, second, and last authors with a few key words from the title. Papers were defined as "suspected" redundant publications if they were found to address the same topic as the "index" article and shared some or most of the elements of methodology, results, or conclusions. The full versions of all suspected papers were retrieved and compared with the index articles. A grading system was developed to define several types of redundant publications: A. "dual"; B. "potentially dual"; C. "salami-slicing." A total of 660 articles were screened. There were 92 index articles (14%) leading to 147 suspected papers found in other journals, representing some potential form of a redundant publication. The vast majority of suspected papers were published within approximately a year of the index paper and were not cited by the latter. Most (69%) of the suspected papers were also published in surgical journals. Only 12 (8.1%) appeared in, or originated from, a "local-foreign" journal. Twenty (13.6%) of the suspected papers met the criteria for dual publications, 50 (34%) for potentially dual publications, and 77 (52.4%) were considered products of salami-slicing. Almost 1 in every 6 original articles published in leading surgical journals represents some form of redundancy. Current on-line search technology provides an effective tool for identifying and tracing such publications, but it is not used routinely as part of the peer review process. Redundancies occur in several well-defined patterns; the phenomenon is widespread, and it cuts across the entire spectrum of surgeons in the United States and abroad. Redundant publications must be recognized not as a mere nuisance but as a real threat to the quality and intellectual impact of surgical publishing.


Giant gastrointestinal stromal tumor, associated with esophageal hiatus hernia.
An 85-year-old woman was admitted to our hospital because of vomiting. An upper gastrointestinal series what showed a large esophageal hiatus hernia, suggesting an association with extrinsic pressure in the middle portion of the stomach. An upper gastrointestinal endoscopic examination showed severe esophagitis and a prominent narrowing in the middle portion of the stomach, however, it showed normal gastric mucosa findings. CT and MRI revealed a large tumor extending from the region of the lower chest to the upper abdomen. From these findings, the tumor was diagnosed as gastrointestinal stromal tumor (GIST), which arose from the gastric wall and complicated with an esophageal hiatus hernia. We performed a laparotomy, however, the tumor showed severe invasion to the circumferential organs. Therefore, we abandoned the excision of the tumor. Histologically, the tumor was composed of spindle shaped cells with marked nuclear atypia and prominent mitosis. The tumor cells were strongly positive for CD34 and c-kit by immunohistochemical examination. From these findings, the tumor was definitely diagnosed as a malignant GIST. As palliative treatment, we implanted a self-expandable metallic stent in the narrow segment of the stomach. The patient could eat solid food and was discharged. In the treatment of esophageal hiatus hernia, the rare association of GIST should be considered.


Effect of tDCS on task relevant and irrelevant perceptual learning of complex objects.
During perceptual learning the visual representations in the brain are altered, but these changes' causal role has not yet been fully characterized. We used transcranial direct current stimulation (tDCS) to investigate the role of higher visual regions in lateral occipital cortex (LO) in perceptual learning with complex objects. We also investigated whether object learning is dependent on the relevance of the objects for the learning task. Participants were trained in two tasks: object recognition using a backward masking paradigm and an orientation judgment task. During both tasks, an object with a red line on top of it were presented in each trial. The crucial difference between both tasks was the relevance of the object: the object was relevant for the object recognition task, but not for the orientation judgment task. During training, half of the participants received anodal tDCS stimulation targeted at the lateral occipital cortex (LO). Afterwards, participants were tested on how well they recognized the trained objects, the irrelevant objects presented during the orientation judgment task and a set of completely new objects. Participants stimulated with tDCS during training showed larger improvements of performance compared to participants in the sham condition. No learning effect was found for the objects presented during the orientation judgment task. To conclude, this study suggests a causal role of LO in relevant object learning, but given the rather low spatial resolution of tDCS, more research on the specificity of this effect is needed. Further, mere exposure is not sufficient to train object recognition in our paradigm.


Comparative aspects of the density and diameter of Haversian canals in the diaphyseal compact bone of man and dog.
By using an original method, the authors injected the system of canals and then studied microscopically their network in the femoral diaphysis of man and dog. In the human bone, the density varies between 1.09 and 2.63 canals per mm2, with an average of 1.83; in dogs the limits of variation are 1.98--2.86 canals per mm2. The canal calibre is of 68.8 microns in man as against 48.5 microns in dogs. Both parameters present a wider variability in the femoral compact bone of man than in dog. By calculation it was found that the canal density in dogs is very significantly increased as compared to man; on the contrary, the diameter presents in dogs very significantly decreased values as compared to those of the diaphyseal compact bone of man.


Recent advances of antibody drug conjugates for clinical applications.
Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug via a chemical linker. After decades of preclinical and clinical studies, a series of ADCs have been widely used for treating specific tumor types in the clinic such as brentuximab vedotin (Adcetris®) for relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, gemtuzumab ozogamicin (Mylotarg®) for acute myeloid leukemia, ado-trastuzumab emtansine (Kadcyla®) for HER2-positive metastatic breast cancer, inotuzumab ozogamicin (Besponsa®) and most recently polatuzumab vedotin-piiq (Polivy®) for B cell malignancies. More than eighty ADCs have been investigated in different clinical stages from approximately six hundred clinical trials to date. This review summarizes the key elements of ADCs and highlights recent advances of ADCs, as well as important lessons learned from clinical data, and future directions.


Can Exhaled Carbon Monoxide Be Used as a Marker of Exposure? A Cross-Sectional Study in Young Adults.
Carbon monoxide (CO) poisoning is a major public health issue worldwide. People are exposed to CO in their daily lives, with one of the common sources of CO being cigarette smoking. Inhalation of CO leads to elevated carboxyhaemoglobin (COHb) levels in the blood and also in exhaled CO concentration. Several factors have been shown to affect COHb concentration and COHb half-life. However, factors affecting exhaled CO concentration and exhaled CO half-life are not well understood. The present study aimed to investigate the potential factors related to baseline exhaled CO concentration and exhaled CO half-life among smokers. A cross-sectional study was conducted between 26 January and 30 June 2019, and young adults were recruited into the study. A total of 74 participants (mean age: 27.1 years, 71.6% males and 28.4% females) attended the study. They were invited to complete a questionnaire, including demographic, physiological, and behavioural factors. Then, exhaled CO measurements were taken. These measurements were taken before and after smoking a single cigarette for smokers and only once for non-smokers. The average baseline exhaled CO concentration was 6.9 ± 4.9 ppm for smokers and 1.9 ± 0.5 ppm for non-smokers. The mean of exhaled CO half-life was around 273.3 min (4.6 h) for smokers. No difference was seen in exhaled CO half-life between light smokers and heavy smokers in the smoking group. Gender and cigarettes smoked weekly affected baseline exhaled CO in smokers. Even though height seemed to positively associate with exhaled CO half-life, the relationship disappeared when adjusting by gender and weight. Therefore, exhaled CO could be used as a marker of CO exposure, but we cannot ignore the factors mentioned in the study. For future study, considering factors related to smoking habits and smoking style are recommended as these may affect total inhaled CO.


Modulation of growth factor/cytokine synthesis and signaling by 1alpha,25-dihydroxyvitamin D(3): implications in cell growth and differentiation.
Distinct from its classic functions in the regulation of calcium and phosphorus metabolism as a systemic hormone, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] is involved in the local control and regulation of cellular growth and differentiation in various tissues, including epidermis (keratinocytes) and bone (osteoblasts and osteoclasts). In this review, the impact of 1alpha,25(OH)(2)D(3) on growth factor/cytokine synthesis and signaling is discussed, particularly as it pertains to bone cells and keratinocytes. 1alpha,25(OH)(2)D(3) not only regulates growth factor/cytokine synthesis but may also alter growth factor signaling. Recently discovered examples for such interactions are the interactions between the vitamin D receptor and the mothers against decapentaplegic-related proteins that function downstream of TGFbeta receptors. Inhibitory effects of 1alpha,25(OH)(2)D(3) on keratinocytes through TGFbeta activation and IL-1alpha, IL-6, and IL-8 suppression may provide a rationale for its beneficial effects in the treatment of hyperproliferative skin disorders, whereas stimulatory effects through the epidermal growth factor-related family members and platelet-derived growth factor may be operative in its beneficial effects in skin atrophy and wound healing. Modulation of cytokines and growth factors by 1alpha,25(OH)(2)D(3) during bone remodeling plays an important role in the coupling of osteoblastic bone formation with osteoclastic resorption to maintain bone mass.


Population panmixia and demographic expansion of a highly piscivorous marine fish Scomberomorus niphonius.
Population structure and demographic history of the Japanese Spanish mackerel Scomberomorus niphonius a highly piscivorous and migratory marine fish, were assessed using mitochondrial DNA control region sequences (n = 720) and microsatellite genotypes at five loci (n = 1331) for samples collected on Japanese coasts from 2001 to 2010. The population structure was panmictic and the haplotype and allele frequencies were temporally stable even during the recent recovery process. Demographic expansion was strongly supported throughout the Pleistocene, suggesting that the oscillating glacial and interglacial climate conditions in the Pleistocene had no substantial impact on the demographic history of S. niphonius.


Therapeutic implications of functional tea ingredients for ameliorating inflammatory bowel disease: a focused review.
Inflammatory bowel disease (IBD) is a chronic gastro-intestinal disorders of unknown etiology. There are several drugs approved for treating IBD patients with active disease, including first-line use of aminosalicylates, and secondary choices of immunomodulators and other therapies. These medications might manage disease symptoms, but have also shown significant side-effects in IBD patients. Tea is the second largest beverage in the world and its main active ingredients including tea polyphenols, polysaccharides and tea pigments have been shown promising anti-inflammatory and antioxidant properties. In this review, we summarize the influence of different tea varieties including green tea, black tea and dark tea as potential nutritional therapy for preventing and treating IBD, and discuss the mechanisms of tea ingredients involved in the regulation of oxidative stress, inflammation, signaling pathways, and gut microbiota that could benefit for IBD disease management. Our observation directs further basic and clinical investigations on tea polyphenols and their derivatives as novel IBD therapeutic agents.


Personalized Reconstruction of Genital Defects in Complicated Wounds with Vertical Rectus Abdominis Myocutaneous Flaps including Urethral Neo-Orifice.
Non-healing extensive wounds in the perineal region can lead to severe soft tissue infections and disastrous complications, which are not manageable with conservative measures. Specifically in recurrent or advanced pelvic malignancies, irradiation often leads to extensive scarring and wound breakdown, resulting in significant soft tissue defects during surgical tumor excision. Among several surgical options to reconstruct the perineum, the transpelvic vertical rectus abdominis myocutaneous (VRAM) flap has proven to be one of the most reliable methods. Specific modifications of this flap allow an individualized procedure depending on the patient's needs. We modified this technique to include the urethral orifice into the skin paddle of VRAM flaps in three patients as a novel option to circumvent urinary diversion and maintain an acceptable quality of life.


Lessons from isolable nickel(I) precursor complexes for small molecule activation.
Small-molecule activation by transition metals is essential to numerous organic transformations, both biological and industrial. Creating useful metal-mediated activation systems often depends on stabilizing the metal with uncommon low oxidation states and low coordination numbers. This provides a redox-active metal center with vacant coordination sites well suited for interacting with small molecules. Monovalent nickel species, with their d(9) electronic configuration, are moderately strong one-electron reducing agents that are synthetically attractive if they can be isolated. They represent suitable reagents for closing the knowledge gap in nickel-mediated activation of small molecules. Recently, the first strikingly stable dinuclear β-diketiminate nickel(I) precursor complexes were synthesized, proving to be suitable promoters for small-molecule binding and activation. They have led to many unprecedented nickel complexes bearing activated small molecules in different reduction stages. In this Account, we describe selected achievements in the activation of nitrous oxide (N(2)O), O(2), the heavier chalcogens (S, Se, and Te), and white phosphorus (P(4)) through this β-diketiminatonickel(I) precursor species. We emphasize the reductive activation of O(2), owing to its promise in oxidation processes. The one-electron-reduced O(2) activation product, that is, the corresponding β-diketiminato-supported Ni-O(2) complex, is a genuine superoxonickel(II) complex, representing an important intermediate in the early stages of O(2) activation. It selectively acts as an oxygen-atom transfer agent, hydrogen-atom scavenger, or both towards exogenous organic substrates to yield oxidation products. The one-electron reduction of the superoxonickel(II) moiety was examined by using elemental potassium, β-diketiminatozinc(II) chloride, and β-diketiminatoiron(I) complexes, affording the first heterobimetallic complexes featuring a [NiO(2)M] subunit (M is K, Zn, or Fe). Through density functional theory (DFT) calculations, the geometric and electronic structures of these complexes were established and their distinctive reactivity, including the unprecedented monooxygenase-like activity of a bis(μ-oxo)nickel-iron complex, was studied. The studies have further led to other heterobimetallic complexes containing a [NiO(2)M] core, which are useful for understanding the influence of the heterometal on structure-reactivity relationships. The activation of N(2)O led directly to the hydrogen-atom abstraction product bis(μ-hydroxo)nickel(II) species and prevented isolation of any intermediate. In contrast, the activation of elemental S, Se, and Te with the same nickel(I) reagent furnished activation products with superchalcogenido E(2)(-) (E is S, Se, or Te) and dichalcogenido E(2)(2-) ligand in different activation stages. The isolable supersulfidonickel(II) subunit may serve as a versatile building block for the synthesis of heterobimetallic disulfidonickel(II) complexes with a [NiS(2)M] core. In the case of white phosphorus, the P(4) molecule has been coordinated to the nickel(I) center of dinuclear β-diketiminatonickel(I) precursor complexes; however, the whole P(4) subunit is a weaker electron acceptor than the dichalcogen ligands E(2), thus remaining unreduced. This P(4) binding mode is rare and could open new doors for subsequent functionalization of P(4). Our advances in understanding how these small molecules are bound to a nickel(I) center and are activated for further transformation offer promise for designing new catalysts. These nickel-containing complexes offer exceptional potential for nickel-mediated transformations of organic molecules and as model compounds for mimicking active sites of nickel-containing metalloenzymes.


Effect of mitigation measures on the spreading of COVID-19 in hard-hit states in the U.S.
State government-mandated social distancing measures have helped to slow the growth of the COVID-19 pandemic in the United States. Many of the current predictive models of the development of COVID-19, especially after mitigation efforts, partially rely on extrapolations from data collected in other countries. Since most states enacted stay-at-home orders towards the end of March, the resulting effects of social distancing should be reflected in the death and infection counts by the end of April. Using the data available through April 25th, we investigate the change in the infection rate due to the mitigation efforts and project death and infection counts through September 2020 for some of the most heavily impacted states: New York, New Jersey, Michigan, Massachusetts, Illinois, and Louisiana. We find that with the current mitigation efforts, five of those six states have reduced their base reproduction number to a value less than one, stopping the exponential growth of the pandemic. We also project different scenarios after the mitigation is relaxed.


Steroid receptors in a group of Brazilian melanoma patients.
Melanoma biopsies from 22 Brazilian patients were evaluated for estrogen (ER), progesterone (PR) and glucocorticoid receptors (GR) by the dextran-coated charcoal method. Fifty percent (11/22) of the tumors exhibited specific estrogen and progesterone binding activities ranging from 5 to 25 fmol/mg protein for ER and from 18 to 200.75 fmol/mg protein for PR; 20/22 (90%) of the biopsies displayed significant quantities of GR, which ranged from 10.0 to 362.5 fmol/mg protein. The incidence and concentration of positive receptors in melanoma samples from Brazilian patients are similar to those of countries with populations of Caucasian origin.


Magnesium phosphate cements for endodontic applications with improved long-term sealing ability.
To characterize three radiopaque Magnesium Phosphate Cements (MPCs) developed for endodontic purposes. Three experimental MPCs containing Bi2 O3 were formulated. The experimental cements, which consisted of mixtures of magnesium oxide with different phosphate salts, were characterized for setting time, injectability, porosity, compressive strength and phase composition. The long-term sealing ability of the experimental MPCs applied in single-rooted teeth as root canal filling material or as sealer in combination with gutta-percha was also assessed using a highly sensitive fluid filtration system. A mineral trioxide aggregate (MTA) cement was used as control. Statistical analysis was performed with two- or three-way analysis of variance (anova) and Tukey's test was used for comparisons. The addition of 10 wt% Bi2 O3 within the composition of the MPCs provided an adequate radiopacity for endodontic applications according to ISO 6876 standard. The reaction products resulting from the MPCs were either struvite (MgNH4 PO4 ·6H2 O) or an amorphous sodium magnesium phosphate. The porosity of the three MPCs ranged between 4% and 11%. The initial setting time of the experimental cements was between 6 and 9 min, attaining high early compressive strength values (17-34 MPa within 2 h). All MPC formulations achieved greater sealing ability than MTA (P < 0.05) after 3 months, which was maintained after 6 months for two of the experimental cements (P < 0.05). These MPCs had adequate handling and mechanical properties and low degradation rates. Furthermore, a stable sealing ability was demonstrated up to 6 months when using the cement both as root filling material and as sealer in conjunction with gutta-percha.


The Effect of Temperature on the Level and Biosynthesis of Unsaturated Fatty Acids in Diacylglycerols of Brassica napus Leaves.
Experiments on the effects of temperature on the levels of unsaturated fatty acids and their rates of desaturation in Brassica napus leaf lipids have shown that significant differences occur in the composition of all diacylglycerols in the leaf between plants grown at high and low temperatures. In the major thylakoid diacylglycerols, monogalactosyl-diacylglycerol and digalactosyldiacylglycerol, not only is there an increase in the level of unsaturation at low temperatures, but there is a change in the balance between molecular species of chloroplastic origin (16/18C) and cytosolic origin (18/18C). Radioactivity tracer data indicate that at low temperatures there are two distinct phases of desaturation in the fatty acids of the major diacylglycerols of these leaves. A rapid phase, which appears in plants grown at low temperatures and results in the desaturation of palmitic acid to hexadecadienoic acid and oleic acid to linoleic acid may explain the high levels of unsaturated fatty acids found in the leaf diacylglycerols from plants grown at low temperatures. The appearance of this rapid phase is controlled by the temperature at which the plant is grown and is not subject to rapid variations in environmental temperature.


Antihypertensive activity of ABBOTT-81282, a nonpeptide angiotensin II antagonist, in the renal hypertensive rat.
ABBOTT-81282, 4-(N-butyl-N-[(2-'-[1H-tetrazol-5yl]biphenyl-4-yl)methyl]ami no) pyrimidine-5-carboxylic acid is a novel nonpeptide angiotensin II (AII) antagonist. In vivo studies were performed to evaluate ABBOTT-81282 for its antihypertensive effect, pharmacological mechanism(s) of action, and cardiovascular safety. In the conscious renal artery-ligated (RAL) hypertensive rat, a model of high renin hypertension, ABBOTT-81282 (1-10 mg/kg p.o. and 0.1-1.0 mg/kg i.v.) lowered mean arterial pressure (MAP) in a dose-dependent manner with the ED30 values of 2.2 mg/kg for p.o. administration and 0.08 mg/kg for i.v. administration. At 10 mg/kg p.o., ABBOTT-81282 lowered blood pressure in the RAL rat (delta MAP 66 +/- 9 mm Hg from control MAP 167 +/- 7 mm Hg, n = 6) to a normotensive level (MAP, 115 +/- 5 mm Hg) for greater than 24 h and did not change heart rate. The i.v. administration of 1 mg/kg of ABBOTT-81282 also produced a sustained, long-lasting decrease (delta MAP 27-52 mm Hg) in blood pressure that was significantly different from the vehicle group at 8 h postdosing (143 +/- 3 mm Hg, n = 4 for ABBOTT-81282 vs. 181 +/- 3 mm Hg, n = 6 for vehicle group, p < 0.01). When blood pressure in the renal hypertensive rat was maximally lowered (delta MAP 72 +/- 9 mm Hg, n = 4) following the 1 mg/kg i.v. dose (cumulative) of ABBOTT-81282, additional administration of captopril (3 mg/kg i.v.) produced no further decline in blood pressure. In the conscious normotensive rat, 10 mg/kg p.o. of ABBOTT-81282 had no effect on basal MAP (119 +/- 3 vs. 115 +/- 4 mm Hg, pre- vs. 3.5 h postdosing, n = 4) and heart rate (364 +/- 18 vs. 363 +/- 14 beats/min, pre- vs. 3.5 h postdosing, n = 4) but inhibited the AII (0.1 micrograms/kg i.v.)-induced increase in MAP by 64-70%, while the MAP responses to norepinephrine (0.3 micrograms/kg i.v.), vasopressin (0.03 IU/kg i.v.) and bradykinin (3 micrograms/kg i.v.) remained intact. ABBOTT-81282 was also administered to conscious normotensive rats (n = 4) instrumented with ECG telemetry transmitters. At an i.v. dose of 10 mg/kg, which is 125 times greater than the i.v. ED30, ABBOTT-81282 caused a minimal decrease (< 14%) in MAP and had no effect on ECG waveforms. These data demonstrate that ABBOTT-81282 is a safe and efficacious antihypertensive agent with selective AII antagonism.(ABSTRACT TRUNCATED AT 400 WORDS)


Digital surface photogrammetry for anthropometric analysis of the cleft infant face.
To analyze the three-dimensional morphology of the cleft infant face with digital surface photogrammetry. Fifty plaster casts of unoperated infants with cleft lip and palate were imaged three-dimensionally with digital surface photogrammetry. Twenty-one standard craniofacial measurements were taken. The plaster casts were divided into 4 groups with unilateral, bilateral, complete, and incomplete clefts of the lip and palate. The measurements were compared with standard values for healthy infants. Significant differences (p < .0025) were found for the alar base width (33% to 55%), the alar base root width (59% to 103%), the width of the nose (7% to 25%), the length of the alar wing (18% to 25%), and the intercanthal (6% to 17%) and biocular (4% to 12%) width, depending on the cleft type. The vertical dimensions of the nose and the upper lip did not differ significantly from the controls. This study describes preliminary data on the cleft infant facial deformity. The obtained results were mainly in agreement with data in the limited literature. Three-dimensional photogrammetry has proven to be reliable and can be applied more readily to potentially uncooperative patients.


Tunable reverse electrodialysis microplatform with geometrically controlled self-assembled nanoparticle network.
Clean and sustainable energy generation from ambient environments is important not only for large scale systems, but also for tiny electrical devices, because of the limitations of batteries or external power sources. Chemical concentration gradients are promising energy resources to power micro/nanodevices sustainably without discharging any pollutants. In this paper, an efficient microplatform based on reverse electrodialysis, which enables high ionic flux through three dimensional nanochannel networks for high power energy generation, is demonstrated. Highly effective cation-selective nanochannel networks are realized between two microfluidic channels with geometrically controlled in situ self-assembled nanoparticles in a cost-effective and simple way. The nano-interstices between the assembled nanoparticles have a role as collective three-dimensional nanochannel networks and they allow higher ionic flux under concentration gradients without decreasing diffusion potential, compared to standard one-dimensional nanochannels. An in-depth experimental study with theoretical analysis shows that the electrical power of the presented system can be flexibly tuned or further optimized by changing the size, material, and shape of the assembled nanoparticles or by the geometric control of the microchannel. This microfluidic power generation system can be readily integrated with existing lab on a chip systems in the near future and can also be utilized to investigate nanoscale electrokinetics.


Nuclear Targeted Peptide Combined With Gambogic Acid for Synergistic Treatment of Breast Cancer.
As a natural compound, gambogic acid (GA) emerged a shining multi-target antitumor activity in a variety of tumors. Whereas its poor solubility and non-specific effect to tumor blocked the clinical application of this drug. Herein, we reported a simple and effective strategy to construct liposome modified with nuclear targeted peptide CB5005N (VQRKRQKLMPC) via polyethylene glycol (PEG) linker to decrease the inherent limitations of GA and promote its anti-tumor activity. In this study, liposomes were prepared by thin film hydration method. The characterization of formulations contained particle size, Zeta potential, morphology and encapsulation efficiency. Further, in vitro cytotoxicity and uptake tests were investigated by 4T1 and MDA-MB-231 cells, and nuclear targeting capability was performed on MDA-MB-231 cells. In addition, the in vivo antitumor effect and biological distribution of formulations were tested in BALB/c female mice. The GA-loaded liposome modified by CB5005N showed small size, good uniformity, better targeting, higher anti-tumor efficiency, better tumor inhibition rate and lower toxicity to normal tissues than other groups. In vitro and in vivo research proved that CB5005N-GA-liposome exhibited excellent anti-tumor activity and significantly reduced toxicities. As a result, CB5005N-GA-liposome nano drug delivery system enhanced the tumor targeting and antitumor effects of GA, which provided a basis for its clinical application.


Percutaneous saphenectomy: a potentially dreadful complication of cutting balloon angioplasty in saphenous vein grafts.
Vessel perforation is an uncommon but potentially life-threatening complication of percutaneous coronary intervention and is often associated with the use of atheroablative devices. While effective management means are currently available, such as PTFE-covered stent, pericardiocentesis, and perfusion balloon, a timely and skillful approach is of paramount importance to solve this dreadful complication. We hereby describe a case of saphenous vein graft (SVG) perforation occurring after cutting balloon angioplasty for in-stent restenosis. Despite the immediate occurrence of cardiac arrest due to massive extravasation of contrast in the mediastinum with pericardial tamponade, deep catheter intubation enabled the deployment of two PTFE-covered stents and subsequent sealing of the leak with repeated inflation of a perfusion balloon, while hemopericardium was drained by pericardiocentesis. This clinical vignette emphasizes the role of optimal backup in order to deploy life-saving devices and successfully manage life-threatening pericardial tamponade due to SVG rupture.


N uptake and distribution in crops: an agronomical and ecophysiological perspective.
The rate of N uptake of crops is highly variable during crop development and between years and sites. However, under ample soil N availability, crop N accumulation is highly related to crop growth rate and to biomass accumulation. Critical N concentration has been defined as the minimum N concentration which allows maximum growth rate. Critical N concentration declines during crop growth. The relationship between critical N concentration and biomass accumulation over the growth period of a crop is broadly similar within major C(3) and C(4) cultivated species. Therefore, the critical N concentration concept is widely used in agronomy as the basis of the diagnosis of crop N status, and allows discrimination between situations of sub-optimal and supra-optimal N supply. The relationship between N and biomass accumulation in crops, relies on the interregulation of multiple crop physiological processes. Among these processes, N uptake, crop C assimilation and thus growth rate, and C and N allocation between organs and between plants, play a particular role. Under sub-optimal N supply, N uptake of the crop depends on soil mineral N availability and distribution, and on root distribution. Under ample N supply, N uptake largely depends on growth rate via internal plant regulation. Carbon assimilation of the crop is related to crop N through the distribution of N between mature leaves with consequences for leaf and canopy photosynthesis. However, although less commonly emphasized, carbon assimilation of the crop also depends on crop N through leaf area development. Therefore, crop growth rate fundamentally relies on the balance of N allocation between growing and mature leaves. Nitrogen uptake and distribution also depends on C allocation between organs and N composition of these organs. Within shoots, allocation of C to stems generally increases in relation to C allocation to the leaves over the crop growth period. Allocation of C and N between shoots and roots also changes to a large extent in relation to soil N and/or crop N. These alterations in C and N allocation between plant organs have implications, together with soil availability and carbon assimilation, on N uptake and distribution in crops. Therefore, N uptake and distribution in plants and crops involves many aspects of growth and development. Regulation of nitrogen assimilation needs to be considered in the context of these interregulatory processes.


Triiodothyronine therapy lowers the incidence of atrial fibrillation after cardiac operations.
Cardiopulmonary bypass results in a euthyroid sick state, and recent evidence suggests that perioperative triiodothyronine (T3) supplementation may have hemodynamic benefits. In light of the known effects of thyroid hormone on atrial electrophysiology, we investigated the effects of perioperative T3 supplementation on the incidence of postoperative arrhythmias. One hundred forty-two patients with depressed left ventricular function (ejection fraction < 0.40) undergoing coronary artery bypass grafting were randomized to either T3 or placebo treatment groups in a prospective, double-blind fashion. Triiodothyronine was administered as a 0.8 micrograms/kg intravenous bolus at the time of aortic cross-clamp removal followed by an infusion of 0.113 micrograms.kg-1.h-1 for 6 hours. Patients were monitored for the development of arrhythmias during the first 5 postoperative days. The incidence of sinus tachycardia and ventricular arrhythmias were similar between groups. Triiodothyronine-treated patients had a lower incidence of atrial fibrillation (24% versus 46%; p = 0.009), and fewer required cardioversion (0 versus 6; p = 0.012) or anticoagulation (2 versus 10; p = 0.013) during hospitalization. Six patients in the T3 group versus 16 in the placebo group required antiarrhythmic therapy at discharge (p = 0.019). Perioperative T3 administration decreased the incidence and need for treatment of postoperative atrial fibrillation.


Radiation-induced effect of adenine (vitamin B4) on mitomycin C activity. In vitro experiments.
The radiation-induced biological behavior of adenine (vitamin B4) was investigated in vitro under various conditions, implementing breast cancer cells (MCF-7 line) as a model. In aerated media (46% OH and 54% O2*-) at pH=7.4, adenine at low concentration (2 micromol) acted as an efficient radiation-protecting agent. At higher concentration, however, it inhibited cytostatic properties with regard to cancer cells. This double-track activity is based on its chemical structure. Similar features of adenine were also observed in air-free (46% OH, 44% e- aq, 10% H) as well as in media saturated with N2O (90% OH, 10% H), but with different efficiencies. In the presence of mitomycin C (MMC), adenine retained its double-track behavior. Hence, adenine and MMC compete for the e- aq, but the electronically excited adenine molecules can transfer electrons to MMC, leading to the additional formation of active MMC-. By implementation of formate for the conversion of OH and H into the transient *COO-, which subsequently transfers electron to MMC, a highest efficiency of MMC- was obtained.


Oxidative stress and medical antioxidant treatment in male infertility.
Oxidative stress (OS) has been recognized as one of the most important cause of male infertility. Despite the antioxidant activity of seminal plasma, epididymis and spermatozoa, OS damages sperm function and DNA integrity. Since antioxidants suppress the action of reactive oxygen species, these compounds have been used in the medical treatment of male infertility or have been added to the culture medium during sperm separation techniques. Nevertheless, the efficacy of such a treatment has been reported to be very limited. This may relate to: (i) patient selection bias; (ii) late diagnosis of male infertility; (iii) lack of double-blind, placebo-controlled clinical trial; and/or (iv) use of end-points that are not good markers of the presence of OS. This review considers the effects of the main antioxidant compounds used in clinical practice. Overall, the data published suggest that no single antioxidant is able to enhance fertilizing capability in infertile men, whereas a combination of them seems to provide a better approach. Taking into account the pros and the cons of antioxidant treatment of male infertility, the potential advantages that it offers cannot be ignored. Therefore, antioxidant therapy should remain in the forefront of preventive medicine, including human reproductive medicine.


Sugar transport in isolated corn root protoplasts.
Isolated corn (Zea mays L.) root protoplasts were used to study sucrose and hexose uptake. It is found that glucose was preferentially taken up by the protoplasts over sucrose and other hexoses. Glucose uptake showed a biphasic dependence on external glucose concentration with saturable (K(m) of 7 millimolar) and linear components. In contrast, sucrose uptake only showed a linear kinetic curve. Sucrose and glucose uptake were linear over a minimum of 1 hour at pH 6.0 and 1 millimolar exogenous sugar concentration. Glucose uptake showed a sharp 42 degrees C temperature optimum, while sucrose uptake showed a lower temperature sensitivity which did not reach a maximum below 50 degrees C. Uptake of both sugars was sensitive to several metabolic inhibitors and external pH. Differences between sucrose and glucose uptake in two different sink tissue (i.e. protoplasts from corn roots and soybean cotyledons) are discussed.


High mobility group box 1 serum levels are increased in Behçet's disease, but not associated with disease activity or disease manifestations.
High mobility group box 1 (HMGB1) is a nuclear protein that acts as an alarmin when released into the extracellular milieu. HMGB1 is a biomarker of active disease in several systemic autoimmune diseases. Behçet's disease (BD) is a systemic inflammatory disorder with a waxing/waning course. The objective of this study is to evaluate serum HMGB1 levels as a possible biomarker for disease activity in BD. A cross-sectional study measuring serum HMGB1 levels was performed in 26 BD patients and 20 healthy controls. The Brazilian version of the simplified BD Current Activity Form (BR-BDCAFs) was used to measure disease activity. Serum HMGB1 levels were higher in patients with active disease [3.82 (2.54-6.11) ng/ml], in patients with BD without active disease but still on therapy [2.76 (1.89-5.78) ng/ml] and in patients in remission without treatment [2.66 (1.86-4.70) ng/ml] than in healthy controls [0.96 (0.59-1.39) ng/ml], P < 0.001. Levels were comparable between BD patients with active disease, BD without active disease but still on therapy and those in remission without treatment (P = 0.432). There was no correlation between serum HMGB1 levels and BR-BDCAF(s) (ρ = 0.195; P = 0.339). No association could be found between serum HMGB1 levels and specific disease involvement or therapy. So serum HMGB1 levels cannot be used as a biomarker in BD. Serum HMGB1 levels are increased in patients with BD as compared with healthy controls. However, no association was found with disease activity, specific organ involvement or therapy in BD.


Fast and efficient electrical-thermal responses of functional nanoparticle decorated nanocarbon aerogels.
The Joule heating characteristics of functional nanoparticle decorated nanocarbon aerogels are systemically investigated in terms of electrical-thermal responses. Studies verify that nanocarbon aerogels are exceptional supporting and electric-conducting monolithic frameworks for nanoparticles, enabling stable and accurate aerogel temperature control via direct electrical heating of the nanocarbon support, and thus have important applications in electro-catalysis, energy storage, carbon capture and sorption.


D-value determinations are an inappropriate measure of disinfecting activity of common contact lens disinfecting solutions.
Determination of a D value for specific test organisms is a component of the efficacy evaluation of new contact lens disinfecting solutions. This parameter is commonly defined as the time required for the number of surviving microorganisms to decrease 1 logarithmic unit. The assumption made in establishing a D value is that the rate of kill exhibits first-order kinetics under the specified conditions. Such exponential kill rates are seen with thermal contact lens disinfection system. A comparison of the death rate kinetics for a variety of chemical contact lens disinfecting solutions was undertaken to ascertain the suitability of D-value determination for these chemical disinfectants. The active agents of these different solutions included hydrogen peroxide, thimerosal, chlorhexidine, tris(2-hydroxyethyl)tallow ammonium chloride, thimerosal, polyaminopropyl biguanide, and polyquaternium-1. The solutions were challenged with 10(6) CFU of either Pseudomonas aeruginosa, Serratia marcescens, or Staphylococcus hominis per ml, and survival rate was determined. This study clearly demonstrates the nonlinear nature of the inactivation curves for most contact lens chemical disinfecting solutions for the challenge organisms. D-value determination is, therefore, an inappropriate method of reporting the biocidal activity of these solutions.


Apoptosis in tumorigenesis and cancer therapy.
Apoptosis is a morphologically and biochemically distinct form of cell death which can be triggered by a variety of extracellular agents during both normal development as well as in adult pathological states. Much progress has recently been made in understanding the molecular pathways which regulate this process as well as new intersections between these. A direct interaction between components of the 'executioner'--the ICE-family of cysteine proteases--and the Bcl-2 family of proteins, which modulate a cell's propensity to undergo apoptosis, has recently been demonstrated. New pathways to cell survival, like the PI3-K/Akt signal transduction pathway, are also providing new clues as to the regulation of cell death by growth factors and extracellular matrix for example. The links which exist between apoptosis and cancer research are several. Genetic alterations in components of the apoptosis pathway occur during tumorigenesis and confer resistance to a variety of physiological (oncogene-induced cell death, loss of adhesion, growth under hypoxia) as well as therapeutic (chemotherapy and radiation) death triggers. Similarly, antineoplastic therapies are thought to induce tumor cell apoptosis, and consequently, common mutations in apoptosis-regulatory genes carry a poor prognosis for the patient. A more detailed understanding of the biochemistry of apoptosis and the ways in which it is disabled in tumors will likely reveal new transformation selective death triggers which stimulate cell death in ways independent of components like p53 and increase the therapeutic window of these drugs in the clinics.


Concentration Dependence of the Antioxidant and Prooxidant Activity of Trolox in HeLa Cells: Involvement in the Induction of Apoptotic Volume Decrease.
Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a hydrophilic analog of vitamin E, is known for its strong antioxidant activity, being a high radical scavenger of peroxyl and alkoxyl radicals. Under particular conditions, Trolox may also exhibit prooxidant properties. The present work aimed at studying the dual antioxidant/prooxidant behavior of Trolox over a wide range of concentrations (from 2.5 to 160 µM) in HeLa cells. In particular, the study addressed the dose-dependent effects of Trolox on the oxidative cell status and vitality of HeLa cells, focusing on the potential role of the vitamin E analog in the induction of one of the first steps of the apoptotic process, Apoptotic Volume Decrease (AVD). In HeLa cells, Trolox showed significant antioxidant activity, expressed as the ability to reduce the endogenous ROS production detected by the ROS-sensitive probe 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA), at low concentrations (range: 2.5-15 µM), but exerted a dose-dependent prooxidant effect at higher concentrations after 24 h exposure. The prooxidant effect was paralleled by the reduction in cell viability due to the induction of the apoptotic process. The dual behavior, antioxidant at lower concentrations and prooxidant at higher concentrations, was evident also earlier after 2 h incubation, and it was paralleled by the isotonic shrinkage of the cells, ascribed to AVD. The use of SITS, known Cl- channel blocker, was able to completely inhibit the Trolox-induced isotonic cell shrinkage, demonstrating the involvement of the vitamin E analog in the alteration of cell volume homeostasis and, in turn, in the AVD induction. In conclusion, the study shed light on the concentration dependence of the Trolox antioxidant/prooxidant activity in HeLa cells and revealed its role in the induction of one of the first events of apoptosis, AVD, at high concentrations.


Personality disorders and premature dropout from psychological treatment for smoking cessation.
The relation between personality disorders and premature dropout (attending half of the sessions or fewer) from a psychological treatment for giving up smoking was examined in a sample of 202 smokers. Percent of premature dropout was significantly higher for smokers with personality disorder in general, specifically for smokers with dependent personality disorder and with Cluster C personality disorder, than in smokers without such psychopathology.


Advances and challenges in the management of advanced fibrosis in nonalcoholic steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common type of chronic liver disease worldwide. From the spectrum of NAFLD, it is nonalcoholic steatohepatitis (NASH) that predominantly predisposes patients to higher risk for development of cirrhosis and hepatocellular carcinoma. There is growing evidence that the risk of progression to cirrhosis and hepatocellular carcinoma is not uniform among all patients with NASH. In fact, NASH patients with increasing numbers of metabolic diseases such as diabetes, hypertension, visceral obesity and dyslipidemia are at a higher risk of mortality. Additionally, patients with higher stage of liver fibrosis are also at increased risk of mortality. In this context, NASH patients with fibrosis are in the most urgent need of treatment. Also, the first line of treatment for NASH is lifestyle modification with diet and exercise. Nevertheless, the efficacy of lifestyle modification is quite limited. Additionally, vitamin E and pioglitazone may be considered for subset of patients with NASH. There are various medications targeting one or more steps in the pathogenesis of NASH being developed. These drug regimens either alone or in combination, may provide potential treatment option for patients with NASH.


A simple non radioactive method for detecting beta-thalassemia/hbe disease: application to prenatal diagnosis.
We have developed allele specific polymerase chain reaction (ASPCR) that allows rapid screening of the beta E-globin and common beta-thalassemia genes in Thailand. These non-radioactive methods are based on the amplification by the polymerase chain reaction of the beta E and beta-thalassemia specific DNA fragments using specific primers. With this approach, both heterozygote and homozygote for the disease could readily be identified on agarose gel electrophoresis of the amplified DNA. We have applied the method for a prenatal diagnosis of beta-thalassemia/HbE disease in a Thai family at the second trimester of pregnancy. The result obtained was comparable to that of conventional dot blot hybridization using radioactive probes. The simplicity, accuracy and non isotopic of the approach make it a highly promising method for a carrier screening and a prenatal diagnosis of this common disorder.


The role of calcitonin in the development and treatment of osteoporosis.
CT is a peptide hormone produced predominantly by thyroid C cells and probably to a lesser extent by extrathyroidal tissues. Although its physiological function has not yet been established, it is a pharmacological inhibitor of osteoclastic bone resorption. There is currently no convincing evidence that naturally occurring or iatrogenic CT deficiency is involved in the pathogenesis of osteoporosis; however, a selective examination of patients with various rates of bone turnover would help to resolve this issue. As a pharmacological inhibitor of bone resorption, CT has potential usefulness in the therapy of osteoporosis. CT has been shown to stabilize or modestly increase indices of cortical and trabecular bone mass and total body calcium when administered to patients with established osteoporosis for periods of 1-2 yr. The increments in bone mass seen in some studies appear to be transient and are likely due to reductions in bone resorption with bone formation remaining unaffected until remodeling spaces are filled. The duration and magnitude of these increases are probably limited by the eventual decline in bone formation as remodeling equilibrium is reestablished. Therefore, reduction in the rate of bone loss with maintenance of the existing skeletal mass, rather than significant sustained increases in bone mass, should be considered the most realistic therapeutic goal with this agent. Whether or not a reduction in the rate of bone loss persists for longer periods needs further evaluation as does the important issue of subsequent fracture rates. The identification of patients with increased bone resorption rates (high turnover osteoporosis) should help provide a basis for more selective treatment of those patients who would be most likely to respond to this form of therapy. Whether there is additional benefit to using intermittent CT concurrently or sequentially with bone formation stimulating agents (coherence therapy) also needs to be explored. CT may also be of benefit in the prevention of osteoporosis, particularly in postmenopausal women who are unable or unwilling to take estrogen replacement. These potential benefits must be weighed carefully against the current cost of CT and the inconvenience of it having to be given by injection, problems which should be solved by future research.


Medullary electrosensory processing in the little skate. II. Suppression of self-generated electrosensory interference during respiration.
1. Previous studies have demonstrated that the resting activity of electrosensory ALLN fibers is modulated by the animal's own respiratory activity and that all fibers innervating a single ampullary cluster are modulated with the same amplitude and phase relationship to ventilation. We demonstrate that ALLN fibers in the skate are modulated in this common-mode manner bilaterally, regardless of receptor group, orientation, or position of the receptor pore on the body surface (Fig. 2). 2. Ascending efferent neurons (AENs), which project to the electrosensory midbrain from the DON, are modulated through a much smaller portion of their dynamic range. AENs give larger responses to an extrinsic local electric field than to the respiratory driving, indicating that a mechanism exists for suppressing ventilatory electrosensory reafference. 3. In paralyzed animals no modulation of resting activity or of responses of extrinsic electric fields could be observed with respect to the animal's respiratory motor commands in the absence of electrosensory reafference. 4. Cells of the dorsal granular ridge (DGR) project to medullary AENs via the DON molecular layer. A majority of proprioceptive DGR neurons are modulated by ventilatory activity, however, in a given fish the modulation is not in the same phase relationship to ventilation among DGR units. 5. The modulation of AENs during respiration was increased following transection of the contralateral ALLN (Fig. 9). Resting activity and responses to excitatory stimuli were inhibited by simultaneous stimulation of the transected contralateral ALLN indicating that a common-mode rejection mechanism is mediated via the commissural interconnections of the DONs.


Arteriovenous anastomoses at the carotid bodies of rats.
In 2 out of 390 carotid bodies of rats arteriovenous anastomoses (AVA) have been found. Both cases belonged to a group of 12 glomera carotici which were prepared using the semithin section technique. The AVA were found in the course of branches of the glomic arteries leaving the main vessel before its entrance into the carotid body tissue. Thus the AVA were placed near but outside of the carotid bodies. Histologically they showed a distinct extension of the tunica media caused by epitheloidly modified smooth muscle cells. Functionally these AVA could act as shunt vessels (Sperrarterien) that would be able to control the blood flow and/or flow distribution through their carotid bodies.


Inhibition of protein synthesis enhances the lytic effects of tumor necrosis factor alpha and interferon gamma in cell lines derived from gynecological malignancies.
Few clinical responses have occurred in preliminary studies using the cytokines tumor necrosis factor alpha (TNF alpha) or interferon gamma (IFN gamma) in cancer patients. This may be related to the observation that many malignant cell lines are resistant to lysis by these cytokines in vitro. Resistance to lysis by TNF alpha or IFN gamma in many cells is controlled by a protein-synthesis-dependent mechanism, such that when protein synthesis is inhibited cells become sensitive to lysis by these cytokines. Because there is some evidence that TNF alpha and IFN gamma act through different lytic mechanisms and are opposed by different resistance mechanisms, we treated a panel of eight cell lines, five derived from human cervical carcinomas (ME-180, MS751, SiHa, HT-3, and C-33A) and three derived from ovarian carcinomas (Caov-3, SK-OV-3, and NIH: OVCAR-3) with both TNF alpha and IFN gamma to determine whether such combination treatment might maximize in vitro cell lysis. Our results showed that pretreatment with IFN gamma followed by exposure to TNF alpha in the presence of protein synthesis inhibitors increased lysis of seven of the eight cell lines above that seen with either TNF alpha or IFN gamma and inhibitors of protein synthesis. Only the cell line C-33A was resistant to lysis by TNF alpha and IFN gamma, when exposed to these agents both alone and in combination with protein synthesis inhibitors. Clinically, combining the cytokines TNF alpha and IFN gamma with protein synthesis inhibitors may maximize the in vivo lytic effects of these cytokines.


Follow My Eye: Using Gaze to Supervise Computer-Aided Diagnosis.
When deep neural network (DNN) was first introduced to the medical image analysis community, researchers were impressed by its performance. However, it is evident now that a large number of manually labeled data is often a must to train a properly functioning DNN. This demand for supervision data and labels is a major bottleneck in current medical image analysis, since collecting a large number of annotations from experienced experts can be time-consuming and expensive. In this paper, we demonstrate that the eye movement of radiologists reading medical images can be a new form of supervision to train the DNN-based computer-aided diagnosis (CAD) system. Particularly, we record the tracks of the radiologists' gaze when they are reading images. The gaze information is processed and then used to supervise the DNN's attention via an Attention Consistency module. To the best of our knowledge, the above pipeline is among the earliest efforts to leverage expert eye movement for deep-learning-based CAD. We have conducted extensive experiments on knee X-ray images for osteoarthritis assessment. The results show that our method can achieve considerable improvement in diagnosis performance, with the help of gaze supervision.


The efficacy of non-fasting ketogenic diet protocol in the management of intractable epilepsy in pediatric patients: a single center study from Saudi Arabia.
To review the characteristics and outcomes of pediatric patients on a ketogenic diet (KD), an established treatment option for individuals with intractable epilepsy, in a tertiary epilepsy center. This retrospective study included pediatric patients diagnosed with intractable epilepsy who had experienced no benefits from at least two appropriately chosen antiseizure medications. All patients were hospitalized, started a KD without fasting, and were observed for complications and tolerance. The etiology of epilepsy, side effects, and KD efficacy on seizure outcomes were also examined. Of 16 children included in the study, nine (56%) experienced significant seizure improvement, with three becoming seizure-free during the KD. Ten patients were fed orally, and six were fed through gastrostomy feeding tubes. Most were on a 3:1 ratio, and nine reached ketosis within the first three days of KD initiation. Initial recurrent hypoglycemia was documented in four patients, and four experienced vomiting and acidosis. Most families complied with the diet, and all of the children gained weight during the study period. Ketogenic diets are an established and effective treatment for childhood epilepsy, with reversible mild adverse effects. A non-fasting KD protocol is a safe and effective option for children with intractable epilepsy.


Hematopoietic changes and altered reactivity to IL-17 in Syphacia obvelata-infected mice.
Pinworm parasites commonly infect laboratory mice with high prevalence even in well-managed animal colonies. Although often considered as irrelevant, these parasites if undetected may significantly interfere with the experimental settings and alter the interpretation of final results. There are a few reports documenting the effects of pinworms on research and the effects of pinworms on the host hematopoiesis have not yet been investigated. In this study we examined the changes within various hematopoietic cell lineages in the bone marrow, spleen, peripheral blood and peritoneal space during naturally acquired Syphacia obvelata infection in inbred CBA mice. The data obtained showed significant hematopoietic alterations, characterized by increased myelopoiesis and erythropoiesis in S. obvelata-infected animals. In order to additionally evaluate if this pinworm infection modifies hematopoietic cells' reactivity, we examined the effect of murine interleukin-17, T cell-derived cytokine implicated in the regulation of hematopoiesis and inflammation, on the growth of bone marrow progenitor cells and demonstrated that bone marrow myeloid and erythroid progenitors from S. obvelata-infected mice displayed altered sensitivity to IL-17 when compared to non-infected controls. Taken together the alterations presented pointed out that this rodent pinworm is an important environmental agent that might significantly modify the hosts' hematopoietic response, and therefore interfere with the experimental settings and alter the interpretation of the final results. However, the results obtained also contributed new data concerning the activity of IL-17 on bone marrow hematopoietic cells, supporting our previous reports that depending on physiological/pathological status of the organism IL-17 exerts differential effects on the growth of progenitor cells.


Phase-Variable Control of a Powered Knee-Ankle Prosthesis over Continuously Varying Speeds and Inclines.
Most controllers for lower-limb robotic prostheses require individually tuned parameter sets for every combination of speed and incline that the device is designed for. Because ambulation occurs over a continuum of speeds and inclines, this design paradigm requires tuning of a potentially prohibitively large number of parameters. This limitation motivates an alternative control framework that enables walking over a range of speeds and inclines while requiring only a limited number of tunable parameters. In this work, we present the implementation of a continuously varying kinematic controller on a custom powered knee-ankle prosthesis. The controller uses a phase variable derived from the residual thigh angle, along with real-time estimates of ground inclination and walking speed, to compute the appropriate knee and ankle joint angles from a continuous model of able-bodied kinematic data. We modify an existing phase variable architecture to allow for changes in speeds and inclines, quantify the closed-loop accuracy of the speed and incline estimation algorithms for various references, and experimentally validate the controller by observing that it replicates kinematic trends seen in able-bodied gait as speed and incline vary.


Synergistic effect of SnO2/ZnWO4 core-shell nanorods with high reversible lithium storage capacity.
High reversible lithium storage capacity is obtained from novel SnO2/ZnWO4 core-shell nanorods. At C/20 (20 h per half cycle) rate, the reversible capacity of SnO2/ZnWO4 core-shell nanorods is as high as 1000 mA h g(-1), much higher than that of pure ZnWO4, SnO2, or the traditional theoretical result of the simple mixture. Such performance can be attributed to the synergistic effect between the nanostructured SnO2 and ZnWO4. The distinct electrochemical activity of ZnWO4 nanorods probably activates the irreversible capacity of the SnO2 nanoparticles. These results indicate that high-performance lithium ion batteries can be realized by introducing the synergistic effect of one-dimensional core-shell nanocomposites.


Risk of coronary heart disease in patients with HIV infection.
The lives of individuals infected with HIV who have access to combination antiretroviral therapy (cART) are substantially prolonged, which increases the risk of developing non-AIDS comorbidities, including coronary heart disease (CHD). In Europe and the USA, individuals with HIV infection have a ∼1.5-fold increased risk of myocardial infarction relative to uninfected individuals. In Africa, the relative risk of myocardial infarction is unknown, but broadened access to life-extending cART suggests that rates of CHD will rise in this and other resource-constrained regions. Atherogenesis in HIV is affected by complex interactions between traditional and immune risk factors. cART has varied, regimen-specific effects on metabolic risk factors. Overall, cART seems to lessen proatherogenic immune activation, but does not eliminate it even in patients in whom viraemia is suppressed. Current strategies to decrease the risk of CHD in individuals infected with HIV include early initiation of cART regimens with the fewest metabolic adverse effects, and careful management of traditional CHD risk factors throughout treatment. Future strategies to prevent CHD in patients with HIV infection might involve the use of HIV-tailored CHD risk-prediction paradigms and the administration of therapies alongside cART that will further decrease proatherogenic HIV-specific immune activation.


Approach to permanent hemodialysis access in obese patients.
Obesity has reached an epidemic in the United States and, not surprisingly, there has been a dramatic increase in obesity-associated comorbidities, complete with a host of new, related surgical challenges. The creation and maintenance of permanent hemodialysis access, particularly autogenous access, is generally considered more difficult in the obese patient because of the increased risk of perioperative complications, as well as a decreased maturation rate. Most of the data documenting these adverse outcomes come from retrospective studies and, therefore, the reliability of the data is somewhat limited, given the inherent selection bias. In the United States, most obese patients dialyze through prosthetic access, despite the national initiatives targeted at maximizing autogenous access. However, it is possible to construct an autogenous access in most patients, including obese patients, presenting for permanent access using proper, diligent preoperative imaging and an aggressive postoperative surveillance protocol until access maturation. This is facilitated by careful preoperative planning and liberal use of multiple diagnostic and therapeutic maneuvers to improve overall access function. In this review, the outcomes associated with permanent hemodialysis access in the obese are discussed and helpful suggestions to facilitate a functional access provided.


[Construction of eag deletion mutant of Bacillus anthracis vaccine strain A16R].
Construction of eag deletion mutant of Bacillus anthracis vaccine strain A16R. To study the function of the gene eag of Bacillus anthracis vaccine strain A16R, according to the sequence of Bacillus anthracis Ames strain, we designed primers and constructed a recombinant plasmid by the spectinomycin resistance cassette, upstream homologous fragment and downstream homologous fragment of eag cloned in tandem in pKSV7. We introduced the recombinant into A16R by electroporation and screened the mutant using the principle of homologous recombination. We checked the mutant using the PCR and proteomics. We constructed the recombinant plasmid successfully and got the eag deletion mutant. PCR results showed the gene eag was deleted; SDS PAGE showed evident differences between prime strain and mutant strain. Two-dimensional gel electrophoresis results displayed three EA1 protein points of prime strain were absent in the mutant strain. We constructed eag deletion mutant of Bacillus anthracis vaccine strain A16R. This research will be helpful to study the functions of eag gene and the other important genes of Bacillus anthracis.


Health-related quality of life and sense of coherence among elderly patients with severe chronic heart failure in comparison with healthy controls.
To describe health-related quality of life (QoL) and sense of coherence (SOC) in a group of elderly people with moderate to severe chronic heart failure and to make comparisons with a healthy sex- and age-matched control group. Patients (n = 94), with a mean age of 81 years, hospitalized for chronic heart failure with New York Heart Association functional classification III to IV were age- and sex-matched to a healthy control group. The instruments used were the 36-Item Short Form Health Survey (SF-36) and SOC. The patients had lower levels of health-related QoL scores (SF-36) but high and similar scores of SOC compared with the controls. There were, however, significant positive correlations between the SOC scores and the emotional dimensions in the SF-36 instrument. The findings from this study indicate that old age and severe chronic heart failure were associated with limited functional abilities and impaired health-related QoL but also with internal resources such as SOC.


The association of a preschool voice education program with changes in yelling frequency.
Voice problems in children can occur as early as infancy. Early onset of voice problems can carry social and academic penalties, and negatively affect voice in adolescence or adulthood. Unfortunately, only 1% of school-aged children receive voice therapy despite a 6 to 24% prevalence of voice disorders in school-aged children. One alternative may be to use a classroom-based voice education curriculum to effectively reduce yelling frequency, the most common behavior associated with phonotrauma-related voice problems in children. A classroom-based voice education curriculum was administered to preschool children by the preschool speech-language pathologists in a university-affiliated program. Classroom teachers provided cueing and reinforcement of curriculum strategies for 8 weeks following the program. Baseline frequencies of participant yelling behaviors were compared with postprogram frequencies. Results demonstrated significant reduction in yelling frequencies from pre- to postprogram, particularly in those judged as high-frequency yellers prior to the program. Important factors for future consideration are discussed.


Developmental Control of CAM in Peperomia scandens.
Experiments were conducted to examine the development of photosynthetic carbon metabolism in Peperomia scandens, a tropical epiphyte. Leaves were sampled during a 10-day period when they were between 30 to 165 days old. P. scandens exhibits a C(3) to CAM-cycling to CAM shift during maturation with the magnitude of CAM increasing with age. Initially, during both day and night, no significant CO(2) uptake or diurnal acid flux was evident. C(3) gas exchange was detected at 41 days of age with a gradual shift towards CAM gas exchange maximized thereafter. An acidity flux of 130 to 150 microequivalents per gram fresh weight was evident by 41 days. Between 40 and 90 days, the leaves shifted their CO(2) uptake pattern from a daytime to a nighttime peak. After 90 days, the leaves remained in CAM. The delta(13)C values became progressively less negative as the leaves matured. In the 30-day-old leaves, the delta(13)C value was -21.1% while in the 165-day-old leaves the delta(13)C value was -18.3%. The time-dependent shift from C(3) to CAM-cycling to CAM in P. scandens does not appear to result from changes in water, light, or temperature regimes since these variables were constant for all leaves sampled.


Flexible Polycaprolactone and Polycaprolactone/Graphene Scaffolds for Tissue Engineering.
Developing bone scaffolds can greatly improve the patient's quality of life by accelerating the rehabilitation process. In this paper, we studied the process of composite polycaprolactone supercritical foaming for tissue engineering. The influence of graphene oxide and reduced graphene oxide on the foaming parameters was studied. The structural and mechanical properties were studied. The scaffolds demonstrated mechanical flexibility and endurance. The co-culturing and live/dead tests demonstrated that the obtained scaffolds are biocompatible. Different composite scaffolds induced various surface cell behaviors. The experimental data demonstrate that composite foams are promising candidates for in vivo medical trials.


Subunit Structure Differences in RNA Polymerase II Purified from Ungerminated versus Germinated Wheat Embryos.
DNA-dependent RNA polymerase II (RNAP II) was purified from wheat embryos germinated for 0, 12, 24, and 36 hours and examined with several polyacrylamide gel electrophoretic systems. A changing electrophoretic pattern of RNAP II was observed on nondenaturing polyacrylamide gels. Subunit structure analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that from ungerminated embryos, RNAP IIA was almost exclusively obtained which has a subunit structure identical to that established for wheat germ RNAP II previously (Jendrisak, Burgess 1977 Biochemistry 16: 1959-1964). Twelve polypeptides with molecular weights x 10(-3) of 220, 140, 42, 40, 27, 25, 21, 20, 17.8, 17.0, 16.3, and 16.0 were routinely found to be associated with the purified enzyme. From embryos germinated for 36 hours, RNAP IIB was almost exclusively obtained which has a largest subunit of 180,000 mol wt instead of 220,000. From embryos germinated for 24 hours, an approximately equimolar mixture of RNAP IIA and IIB was obtained. Peptide maps of the 220,000 and 180,000 mol wt polypeptides of RNAP IIA and IIB were virtually identical, indicative of a precursor-product relationship for the two polypeptides. In addition to these results, SDS-PAGE indicated that the stoichiometry of the 27,000 mol wt polypeptide increased at the expense of the 25,000 mol wt polypeptide during germination and concomitantly with the appearance of the 180,000 molecular weight polypeptide. No modifications (e.g. gain, loss, or altered mobilities on analytical gels) in any of the other RNAP II subunits were observed in enzyme purified from embryos after various times of germination as determined by a variety of electrophoretic analyses under denaturing conditions.


The protection of long chain polyunsaturated fatty acids by melatonin during nonenzymatic lipid peroxidation of rat liver microsomes.
The in vivo and in vitro effects of melatonin (N-acetyl-5-methoxytryptamine) on lipid peroxidation of long chain polyunsaturated fatty acids (PUFA) located in rat liver microsomes were determined. The effect of intraperitoneal administration of melatonin (10 mg/kg weight/24 hr) on ascorbate-Fe++ induced lipid peroxidation of isolated rat liver microsomes was first examined. The ascorbate induced light emission in hepatic microsomes was inhibited by melatonin treatment [control group: 10.714 +/- 0.894; melatonin group: 3.162 +/- 0.515, counts per minute (cpm) x 10(-5)]. Significant differences in the content of arachidonic C20:4 n-6 and docosahexaenoic acid C22:6 n-3 were observed when control microsomes were lipid peroxidized in the presence of ascorbic acid. These changes were less pronounced in liver microsomes isolated from melatonin treated rats. In vitro assays showed that after incubation of rat liver microsomes in an ascorbate-Fe++ system, at 37 degrees C for 210 min, the total cpm originated from light emission (chemiluminescence) was found to be lower in those membranes incubated in the presence of melatonin. The fatty acid composition of total lipids isolated from rat liver microsomes was substantially modified when subjected to nonenzymatic lipid peroxidation with a considerable decrease of docosahexaenoic acid 22:6 n-3 and arachidonic acid 20:4 n-6. The inhibition of the lipid peroxidation process evaluated as chemiluminescence (total cpm at selected times) was melatonin concentration dependent. Melatonin, at a concentration 1.2 mm, inhibited almost completely the lipid peroxidation process. Arachidonic and docosahexaenoic acids were more affected than docosapentaenoic acid during the lipid peroxidation process. Not all fatty acids were equally protected after the addition of melatonin to the incubation medium. Our results indicate that melatonin may act in vivo and in vitro as an antioxidant protecting long chain PUFA present in rat liver microsomes from the deleterious effect by a selective mechanism that reduces the loss of docosahexaenoic and arachidonic acids.


Occupational exposures and adverse pregnancy outcomes among nurses: a systematic review and meta-analysis.
The nursing profession has been associated with several adverse pregnancy outcomes. However, the associations between occupational exposures and adverse pregnancy outcomes among this group have not been systematically examined. This review collates all epidemiological evidence to examine the strength of associations and consistency among eligible studies. A computer search of EMBASE and PubMed from 1966 through August 2009 was performed, followed by a search of reference lists of relevant studies and narrative reviews Fourteen studies explored the relation between anesthetic gases and spontaneous abortion, 8 the relation between anesthetic gases and congenital malformations, 7 the relation between chemotherapy agents and congenital malformations, and 4 the relation between shift work and spontaneous abortion. In the random-effects models the summary odds ratio (OR) was moderately elevated for all the relations: OR = 1.27, 95% confidence interval (CI) 0.99-1.63 for anesthetic gases and spontaneous abortion. The summary OR was between 1.05 and 1.09 in high-quality studies, registry-based studies, and cohort studies: OR = 1.33, 95% CI 1.09-1.68 for anesthetic gases and congenital malformation. The summary OR was between 0.97 and 1.22 for high-quality studies, registry-based studies, and cohort studies: OR = 1.35; 95% CI 0.91-2.01 for chemotherapy agent and spontaneous abortion. The summary OR was between 1.34 and 1.69 for high-quality studies, registry-based studies, and cohort studies: OR = 1.44, 95% CI 1.06-1.95 for shift work and spontaneous abortion. Nurses were found to be at increased risk of adverse pregnancy outcomes, but the strength of association was weaker in the well-designed studies. The significance of the findings is limited by the number and heterogeneity of the studies.