Influenza ("Bird Flu"), inflammation and anti-inflammatory/analgesic drugs.
The spectre of an influenza pandemic is being widely mooted. Most of the strategies explored to date for controlling or treating the condition have centred on controlling the spread of the infection, the use of vaccines or anti-viral agents. There has been relatively little discussion about treating the lung and systemic inflammatory reactions that occur during influenza infection. In this review a range of therapeutic agents are proposed to treat the inflammatory reactions, principally in the lung as well as the systemic cytokine-mediated immuno-inflammatory reactions that may be a major cause of the morbidity and mortality associated with influenza infections. Among these are pentoxifylline, the statins, the macrolide antibiotics (e.g. azithromycin, clarithromycin, erythromycin), resveratrol (a component of wine and fruits with inhibitory effects on influenza virus replication) and nutraceuticals (including those that contain flavonoids, the marine oils eicosapentanoic and docosanoic acids or the green-lipped mussel extract, Liprinol which may by virtue of the inhibitory effects on the production or actions of pro-inflammatory cytokines, be useful for their anti-inflammatory actions. The efficacy, mode of actions and side effects of non-steroidal anti-inflammatory drugs (NSAIDs) are considered. There are a number of issues relating to their use in treating the inflammatory reactions in the respiratory tract. Among these are the development of gastro-intestinal ulcers and bleeding and hepato-renal reactions in patients that may because of severe systemic inflammation be prone to the development of these adverse reactions. There are also theoretical issues concerning the impact of COX-1 mediating reduction in prostaglandin and increased cytokine production that might have some negative consequences for respiratory inflammation.In conclusion, further consideration should be given to exploring the actions of these anti-inflammatory agents to control the respiratory inflammatory in influenza infections which can have serious consequences for the outcome of the infection.


Prospective study evaluating the effect of mifepristone on E-cadherin expression in villi in early pregnancy.
E-cadherin plays an important regulatory role in implantation, embryo development and placentation. This study aimed to determine the effect of mifepristone on E-cadherin expression in human villi in early pregnancy. Forty healthy women seeking elective pregnancy termination at 5-7 weeks of gestation were recruited. Of these, 22 women chose medical termination (mifepristone-treated group) and took 25mg mifepristone every 12h for 3 days and 600μg buccal misoprostol on the morning of the fourth day. The other 18 women underwent vacuum aspiration (control group). Following collection of villi, E-cadherin protein expression was assessed by immunohistochemical analysis, and E-cadherin mRNA expression was assessed by reverse transcription-polymerase chain reaction. E-cadherin protein expression was significantly higher (p<0.05) in villous cytotrophoblast cells in the mifepristone-treated group compared with the control group. E-cadherin mRNA expression was also significantly higher (p<0.01) in the mifepristone-treated group compared with the control group. E-cadherin expression in villi may be involved in mifepristone-induced pregnancy termination.


Synthesis and dynamic structure of multinuclear Rh complexes of porphyrinoids.
Large porphyrinoids with three Rh(CO)2 groups at their dipyrrin units shows two-step metal transposition through the macrocycle in solution and the equilibrium between the C3v-isomer and the Cs-isomer depends on the solvent polarity.


Activity increases quantal size at the frog neuromuscular junction.
Two h of nerve stimulation at 10 Hz or of elevated spontaneous release in hypertonic solution increased the size of miniature end-plate potentials (m.e.p.p.'s) and currents at the frog neuromuscular junction, probably by increasing the amount of acetylcholine in a quantum. Increases in quantal size may modulate synaptic transmission.


Direct surgical attack on pontine and rhombencephalic lesions.
The introduction of lasers in neurosurgery in 1976 can be considered as a major contribution to gaining access to "untouchable" areas of the brain. This immaterial instrument provides for precise cutting at low penetration depth in surrounding tissues and may carbonize, and thus remove, layers not to be touched because of their highly sensitive vicinity. From a total of 794 patients experiencing the advantages of laser surgery (1976-1984), a series of 12 children with lower brainstem tumors is presented. Intraoperative instability of vital functions was absent throughout, leaving the patients without deterioration of their initial neurological condition. Given appropriate handling and adequate experience, the laser is a singularly helpful surgical tool for gaining access to areas hitherto barred to surgery.


Tyrosine kinase 2 - Surveillant of tumours and bona fide oncogene.
Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family, which transduces cytokine and growth factor signalling. Analysis of TYK2 loss-of-function revealed its important role in immunity to infection, (auto-) immunity and (auto-) inflammation. TYK2-deficient patients unravelled high similarity between mice and men with respect to cellular signalling functions and basic immunology. Genome-wide association studies link TYK2 to several autoimmune and inflammatory diseases as well as carcinogenesis. Due to its cytokine signalling functions TYK2 was found to be essential in tumour surveillance. Lately TYK2 activating mutants and fusion proteins were detected in patients diagnosed with leukaemic diseases suggesting that TYK2 is a potent oncogene. Here we review the cell intrinsic and extrinsic functions of TYK2 in the characteristics preventing and enabling carcinogenesis. In addition we describe an unexpected function of kinase-inactive TYK2 in tumour rejection.


Determination of Residence Time Distribution in a Continuous Powder Mixing Process With Supervised and Unsupervised Modeling of In-line Near Infrared (NIR) Spectroscopic Data.
Successful implementation of continuous manufacturing processes requires robust methods to assess and control product quality in a real-time mode. In this study, the residence time distribution of a continuous powder mixing process was investigated via pulse tracer experiments using near infrared spectroscopy for tracer detection in an in-line mode. The residence time distribution was modeled by applying the continuous stirred tank reactor in series model for achieving the tracer (paracetamol) concentration profiles. Partial least squares discriminant analysis and principal component analysis of the near infrared spectroscopy data were applied to investigate both supervised and unsupervised chemometric modeling approaches. Additionally, the mean residence time for three powder systems was measured with different process settings. It was found that a significant change in the mean residence time occurred when comparing powder systems with different flowability and mixing process settings. This study also confirmed that the partial least squares discriminant analysis applied as a supervised chemometric model enabled an efficient and fast estimate of the mean residence time based on pulse tracer experiments.


Organic cation transporter 2 (SLC22A2), a low-affinity and high-capacity choline transporter, is preferentially enriched on synaptic vesicles in cholinergic neurons.
Organic cation transporters (OCTs) are expressed mainly in the kidney and liver. OCTs transport intrinsic organic cations, including monoamine, dopamine, serotonine and choline, across the plasma membrane. Here, we demonstrate that OCT2 (SLC22A2) is expressed in cholinergic neurons, motoneurons in the anterior horn of the spinal cord, and is implicated in acetylcholine (Ach) recycling in presynaptic terminals. Application of rabbit anti-peptide antibody revealed that OCT2 was expressed in the anterior horn of the spinal cord. Double immunostaining of muscle sections with anti-OCT2 and alpha-bungarotoxin (BTX) revealed that OCT2 was localized in the neuromuscular junctions (NMJs). Immunoelectron microscopy revealed that OCT2 was localized both in synaptic vesicles (SVs) in presynaptic terminals around the motoneurons (C-terminals) and in SVs in nerve terminals in NMJs. The similarity in the distribution of OCT2 in cholinergic neurons and that of vesicular acetyl choline transporter (VAchT), and the fact that OCT2 can transport choline suggest that OCT2 could work as a low-affinity and high-capacity choline transporter at presynaptic terminals in cholinergic neurons in a firing-dependent manner.


The contracted plasma volume syndromes (relative polycythaemias) and their haemorheological significance.
Relative polycythaemia is a general term which includes patients with a normal red cell mass but a contraction of the plasma volume as the cause for the polycythaemia. The relative polycythaemias can broadly be divided into two groups. Firstly, relative polycythaemia may be due to a primary loss of plasma volume due to dehydration, capillary leak or hypo-oncotic pressure. Secondly, relative polycythaemia may be due to a primary contraction of the vascular compartment (i.e. reduced venous compliance). It is this second group which is the least understood and is analysed in detail in this review. In general, this group of polycythaemias is secondary to exogenous or endogenous stress and is mediated via the sympathetic nervous system. Hypoxia, smoking, neurological disorders, myocardial infarction and acute psychological stress have all been demonstrated as possible factors. In many cases of chronic stress polycythaemias aetiological factors may be identified, whereas in others the term idiopathic is probably appropriate. There appears to be a relationship between the idiopathic stress polycythaemias, hypertension and psychological stress. Other patients may have primarily a disorder of blood volume control involving the autonomic nervous system and its receptors. The haemorheological significance of relative polycythaemia and its management are discussed. Treatment is generally dictated by the underlying cause. In stress polycythaemias the stimulus should be removed as far as possible. However, in some patients with chronic idiopathic stress polycythaemia, regular venesection may be required to maintain the venous haematocrit at an appropriate level.


Investigation of water-soluble inclusion complex of hypericin with β-cyclodextrin polymer.
A water-soluble inclusion complex of hypericin (HY) with β-cyclodextrin polymer (CDP) was achieved by supramolecular interactions between HY and CDP. The inclusion complex (HY-CDP) was characterized by (1)H NMR, FTIR, and UV-vis spectroscopies. Compared with HY, the water-solubility of HY-CDP was greatly enhanced because of the water-soluble CDP host. The mole ratio of β-cyclodextrin (β-CD) unit in CDP to HY was determined as 2:1. At 25 °C, the dissociated constant of HY-CDP was measured as 1.47×10(-7) mol L(-1) by UV-vis spectroscopy. In the formation of inclusion complexes, CDP could overcome the β-CD drawbacks - such as the poor water-solubility and the restriction of single cavity size, indicating it was able to use as a universal solubilizer for pharmaceutical application.


[Supplying surgery blocs in red cell concentrates: a collective approach to improve practices].
The need to adapt red blood cells concentrates management in surgery blocs and resuscitation to the changes of the legal framework has lead to a collective approach to improve practices. Gathered by the regional hemovigilance coordinators of the Drass Ile-de-France (regional office of health and social actions), representatives of doctors' ordering transfusions and hemovigilance correspondents of the Assistance publique-Hôpitaux de Paris and representatives of the EFS (French blood establishment) Ile-de-France, together with representatives of the Afssaps (French health products safety agency), have coordinated an assessment of local transfusion practices in surgery blocs and resuscitation that have to be compliant. Each hospital then offered local improvement actions, approved by regional and national instances. We present this original and collective approach of assessing practices leading to offers that both respond to a legal framework and improve blood products flows without damaging transfusion security.


[Node-positive prostate cancer. Value of radical prostatectomy].
The current review article critically discusses the potential advantages and disadvantages of radical prostatectomy in patients with locally advanced lymph node-positive prostate cancer. It is the purpose of the manuscript to develop a therapeutic algorithm for management of these patients to achieve optimal oncological and functional results. Based on the data in the literature radical prostatectomy as part of a multimodality approach seems to be indicated in the following clinical scenario: limited intrapelvic lymph node metastasis without bulky disease; complete resectability of the primary cancer and metastases by extended radical prostatectomy and extended pelvic lymphadenectomy; inclusion of the patient in a multimodality approach; life expectancy > 10 years. In patients with extensive locally advanced PCA or large pelvic metastases, radical prostatectomy might be indicated to improve local cancer control and to prevent significant local and supravesical complications. In these cases, the indication for extensive surgery includes radical cystoprostatectomy and should be discussed in an interdisciplinary tumour board.


Effects of Riyadh cement industry pollutions on some physiological and morphological factors of Datura innoxia Mill. plant.
Cement factory emissions into air cause serious air pollution and affect the plant and animal life in the environment. Herein, we report the effects of cement industry emissions (O3, SO2 and NO2) in air, as pollutants, at Riyadh City on Datura innoxia Mill. plant. Morphological characters including plant height, leaves area and number, fresh and dry weight of shoot and root systems of D. innoxia showed a significant reduction from their normal control plants as a response to exposure to pollutant emissions. Chlorophyll and carotenoid contents recorded reductions in values compared to control plant, and the lowest values of chlorophyll A, B, total chlorophyll, carotenoids and total pigments were 0.431, 0.169, 0.60, 0.343 and 0.943 mg/g respectively at a distance of 1-5 m from the cement factory in fruiting stage. These changes in values may be attributed to a probable deceleration of the biosynthetic process rather than degradation of pigments. Further D. innoxia showed a significant (P < 0.01) reduction in non-reducing and total sugars, protein and total lipid contents compared with the control plant. The root system recorded the lowest values of reducing sugars (0.350 mg/g f. wt.), non-reducing sugars (0.116 mg/g f. wt.), total sugars (0.466 mg/g f. wt.), protein content (0.931 mg/g f. wt.) and total lipids content (0.669 mg/g f. wt.) in fruiting stage at a distance of 1-5 m from the cement factory. The peroxidase activity of shoot and root systems of the studied plant was also significantly higher than those of control plant. Thus a highest value of (29.616 units/g f. wt.) peroxidase activity was recorded in vegetative stage of shoot system at a distance 1-5 m from the cement factory. Results of the study indicated that cement industry emission strongly influence the physiology and morphology of date palm D. innoxia which contribute date fruits, a staple food in the Arab world.


Restoring activity in the thalamic reticular nucleus improves sleep architecture and reduces Aβ accumulation in mice.
Sleep disruptions promote increases of amyloid β (Aβ) and tau in the brain and increase Alzheimer's disease (AD) risk, but the precise mechanisms that give rise to sleep disturbances have yet to be defined. The thalamic reticular nucleus (TRN) is essential for sleep maintenance and for the regulation of slow-wave sleep (SWS). We examined the TRN in transgenic mice that express mutant human amyloid precursor protein (APP) and found reduced neuronal activity, increased sleep fragmentation, and decreased SWS time as compared to nontransgenic littermates. Selective activation of the TRN using excitatory DREADDs restored sleep maintenance, increased time in SWS, and reduced amyloid plaque load in both hippocampus and cortex. Our findings suggest that the TRN may play a major role in symptoms associated with AD. Enhancing TRN activity might be a promising therapeutic strategy for AD.


Bisdemethoxycurcumin suppresses MCF-7 cells proliferation by inducing ROS accumulation and modulating senescence-related pathways.
Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin present in the phenolic components extracted from the dried rhizome of Curcuma longa L. BDMC demonstrated potential chemotherapeutic activities but the underlying mechanisms have not been fully clarified. In the present study, the role of reactive oxidative species (ROS) in the anti-cancer effects of BDMC was investigated. MCF-7 cells were exposed to BDMC, and then the cell proliferation, colony formation ability and cell cycle profile were analyzed. Cellular ROS level was determined by flow cytometry and fluorescent microscope observation using specific fluorescent probes. Mitochondrial membrane potential (ψm) was assessed using JC-1. In addition, effects of BDMC on senescence-related molecules were analyzed by western blot assay. BDMC significantly inhibited MCF-7 breast cancer cell proliferation, while a rapid rise of the intracellular ROS level accompanied with a reduction of Dym were observed. In addition, BDMC activated the pro-apoptotic protein p53 and its downstream effector p21 as well as the cell cycle regulatory proteins p16 and its downstream effector retinoblastoma protein (Rb). All of these BDMC-induced effects were counteracted with the pre-incubation of the antioxidant N-acetylcysteine (NAC). These results suggested that BDMC-induced ROS accumulation may contribute to its inhibitory effect on MCF-7 cell viability through regulation of p53/p21 and p16/Rb pathways.


Sample application position and the resolution of protein separation on the Beckman Microzone Electrophoretic System.
Many clinical laboratories use the Beckman Microzone electrophoretic system (Beckman Instruments Inc. Fullerton, CA 92634) for serum protein separation. Although detailed instruction is supplied in the manufacturer's manual (1) for protein separation, the effect of different sample application positions on the cellulose acetate membrane is not discussed. We have processed the serum specimen in various application positions and found that there is a definite relationship between the resolution of fractionated protein bands and the application position, particularly with specimens from patients with monoclonal gammonpathies. The resolution of the protein bands increases as the sample is applied closer to the anode end of the cellulose acetate strip. Although studies were carried out on the Beckman electrophoretic system, a similar application effect may be anticipated with other electrophoretic systems.


Coordination between microbiota and root endodermis supports plant mineral nutrient homeostasis.
Plant roots and animal guts have evolved specialized cell layers to control mineral nutrient homeostasis. These layers must tolerate the resident microbiota while keeping homeostatic integrity. Whether and how the root diffusion barriers in the endodermis, which are critical for the mineral nutrient balance of plants, coordinate with the microbiota is unknown. We demonstrate that genes controlling endodermal function in the model plant Arabidopsis thaliana contribute to the plant microbiome assembly. We characterized a regulatory mechanism of endodermal differentiation driven by the microbiota with profound effects on nutrient homeostasis. Furthermore, we demonstrate that this mechanism is linked to the microbiota's capacity to repress responses to the phytohormone abscisic acid in the root. Our findings establish the endodermis as a regulatory hub coordinating microbiota assembly and homeostatic mechanisms.


Assessment of the nervous system.
This article describes the examination of the neurologic and ophthalmic systems in ruminants. Neuroanatomy with respect to lesion localization is reviewed. Pertinent age and species differences are addressed. The practical aspects of assessing the neurologic system are stressed, and the reader is directed to other sources of information for assistance in determining the differential diagnosis and therapy of neurologic disease.


Occlusion of Fontan fenestrations using Amplatzer septal occluder.
The objective of the study is to assess efficacy and safety of the Amplatzer septal device for percutaneous occlusion of Fontan fenestration. Fenestration improves postoperative outcomes in children undergoing Fontan repair. Many of these fenestrations close spontaneously; persistent fenestrations ultimately cause desaturation and can be a potential cause of paradoxical embolism. This is a retrospective review of 26 consecutive patients who underwent transcatheter closure of Fontan fenestration in a tertiary cardiac center in Kuwait. After assessment of hemodynamic suitability for fenestration closure, appropriate balloon sizing of fenestration was obtained. The median age was 9.2 years (range = 1.5-18.3 years). Occlusion was accomplished using a 4-7 ml single Amplatzer septal device in 12 patients and 8-13 ml devices in the other 13 patients; 2 devices were deployed in one patient. Median fluoroscopic and procedure times were 22 and 143.5 min, respectively. One immediate complication was the embolization and successful retrieval of the Amplatzer duct occluder. The fenestration was subsequently occluded by Amplatzer septal device. A 100% occlusion rate of fenestration was achieved in both lateral tunnel and extracardiac conduit types of Fontans. Mean (SD) arterial oxygen saturation increased from 84.7% (4.7) to 95.2% (1.7, P < 0.001) 10 min after deployment of the occluder; Fontan mean circuit pressure had a minimal acceptable increment from 12.9 mmHg (3.2) to 14.6 mmHg (2.6, P < 0.001). No complications or device failures were seen during follow up. The Amplatzer septal occluder device is effective in closing both Fontan fenestrations. Longer single or dual anti-platelet therapy may be considered to prevent thrombotic events. Long-term outpatients follow up with transthoracic echocardiographic monitoring for systemic venous congestion or thrombosis is warranted.


Rigid versus soft catheter for less invasive surfactant administration: A crossover randomized controlled manikin trial.
We compared surfactant administration with a rigid versus soft catheter in a manikin simulating an extremely preterm infant. Randomized controlled crossover (AB/BA) trial. Fifty tertiary hospital consultants and pediatric residents. The primary outcome was the time of device positioning. The secondary outcomes were the success of the first attempt, the number of attempts, and the participant's opinion. Median time of device positioning was 19 s (interquartile range [IQR]: 15-25) with rigid catheter and 40 s (IQR: 28-66) with soft catheter (p < 0.0001). Success at first attempt was 92% with rigid catheter and 74% with soft catheter (p = 0.01). Median number of attempts was 1 (IQR: 1-1) with rigid catheter and 1 (IQR: 1-2) with soft catheter (p = 0.009). Participants found the rigid catheter easier to use (p < 0.0001). In a preterm manikin model, using a rigid catheter for less invasive surfactant administration was quicker and easier to use than a soft catheter.


Usefulness of a simple photometric determination of chymotrypsin activity in stools--results of a multicentre study.
The usefulness of a new photometric test for the determination of chymotrypsin activity in stools was evaluated in a multicentre study. By release of the enzyme from stool particles with a cationic detergent solution after, in most cases, 3 min of homogenization, a photometric measurement of the enzyme activity is possible both in the clear supernatant after centrifugation and in the diluted stool homogenate. The precision of the activity measurement in stool samples with pathologically lowered and normal chymotrypsin activity is good both for in-series (CV = 2.6%, scatter 0.6-5.7%) and for day-to-day determinations (CV = 7.2%, scatter 3.9-13.9%). The results obtained by the photometric determination also exhibit a close correlation with the values measured by pH-stat titrimetry (r = 0.901). The sample-preparation system with a sample-metering chamber is easy to use and gives good agreement with determinations in which the sample metering was done by weighing out the stool (r = 0.961). The photometric test for detection of exocrine pancreatic insufficiency is easy to perform, inexpensive and does not place any undue stress on the patient.


[Serum concentration and tubular resorption of sodium and chloride in patients with chronic renal disease].
Tubular transport of sodium (TNa+) and chloride (TCl-) is decreased in patients with chronic kidney disease. The decrease of TCl- is relatively lower than that of TNa+. These changes of tubular transport of Na+ and Cl- participate on the development of acid base disturbance in patients with chronic kidney disease and with their glomerular filtration rate lower than 0.5 ml/s/1.73 m2.


Imbalance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in toluene diisocyanate-induced asthma.
Toluene diisocyanate (TDI)-induced asthma is an inflammatory disease of the airways characterized by airway remodelling due, at least in part, to an excess of extracellular matrix deposition in the airway wall. The ratio of matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) may be a marker of the balance between airway tissue destruction and repair. We determined whether an imbalance of the MMP-9 : TIMP-1 molar ratio is present before and/or after challenge with TDI. We used a murine model of TDI-induced asthma to evaluate the MMP-9 and TIMP-1 balance in the lung. The expression of MMP-9 and TIMP-1 mRNAs and proteins in the lungs increased at 7 h after TDI inhalation and continued for up to 72 h. Immunohistochemical and immunocytological analyses in the lungs of TDI-exposed mice revealed increases of immunoreactive MMP-9 and TIMP-1. There were significant correlations between the levels of MMP-9 or TIMP-1 and the number of neutrophils, lymphocytes, or eosinophils. The molar ratio of MMP-9/TIMP-1 significantly decreased at 7 h after TDI inhalation and continued up to 72 h. These data suggest that TDI-induced asthma may be associated with an imbalance between MMP-9 and TIMP-1, which could be useful as a marker of airway inflammation and airway remodelling in this disease.


The peripheral chromosome scaffold, a novel structural component of mitotic chromosomes.
Using an original high-salt extraction protocol, we observed a novel chromosome substructure, referred to as the peripheral chromosome scaffold. This chromosome domain contained the perichromosomal layer proteins pKi-67, B23/nucleophosmin and fibrillarin, but no DNA fragments (i.e., the loop domain bases were not associated with the peripheral scaffold). Modern models of chromosome organization do not predict the existence of a peripheral chromosome scaffold domain, and thus our observations have conceptual implications for understanding chromosome architecture.


Determination of roadside noise reduction effectiveness of Pinus sylvestris L. and Populus nigra L. in Erzurum, Turkey.
This study was carried out to determine the noise-reduction effectiveness of the Pinus sylvestris L. and Populus nigra L. trees along the E-80 State highway in Erzurum-Turkey. Noise values were taken at three measurement points; open (without trees and taken as control), the urban forests of pure P. sylvestris L. and P. nigra L. areas, and at four different distances; 0 (near the noise source), 25, 50 and 75 m from the noise source. At the distance of 25 m from the source, the noise value was 78.5 dB(A) in the control area, which was reduced 75.5 dB(A) and 69.2 dB(A) in the P. nigra L. and P. sylvestris L. areas, with the reduction rates of 24.7 and 31% compared to the control, respectively. This value was 69.6, 67.1 and 64.3 at the distance of 50 m and 64.9, 62.5 and 59.2 at 75 m for the naked, P. nigra L. and P. sylvestris L. areas, respectively. From the results of the study, it was suggested that for the noise pollution from the traffic flow on the roads, in especially the big cities, noise reduction zones with suitable width and plant species should be formed along the main arteries of the cities.


[Clinical results after three years use of matrix-associated ACT for the treatment of osteochondral defects of the knee].
The aim of this study was to examine the clinical results after the treatment of osteochondral defects of the knee with autologous bone grafting and matrix-supported autologous chondrocyte transplantation (ACT). In this study 13 patients with osteochondral defects of the knee (12 femoral, 1 tibial) with OCD ICRS grade IV or ICRS grade IV B were included. The osteochondral defects were reconstructed simultaneously with autologous monocortical cancellous bone cylinders or chips from cancellous bone and matrix-supported autologous chondrocyte transplantation (CaReS). Data were analysed in accordance with the ICRS criteria and the Brittberg score. Patients were followed up to 36 months after the operation. The average age of the patients was 34.9 (16 - 47) years at the time of surgery. The size of the defect was 8.1 (3.8 - 13.5) cm(2). The subjective and objective IKDC scores, the Brittberg and the ICRS function score were statistically significantly improved during the observation time. In one patient the transplantation failed and another patient was not available for the follow-up at 36 months. The objective IKDC score and the ICRS function score increased from 0/13 (0 %) to 11/12 (91.7 %) in categories A and B, or I and II, respectively, after 3 years. At this point of time 83.4 % (10/12) of the patients voted the treatment as excellent or good. The subjective IKDC score improved from 38.4 (+/- 12.7) preoperatively to 66.1 (+/- 17.0) after 3 years. The treatment of osteochondral defects of the knee with autologous bone grafting and matrix-supported autologous chondrocyte transplantation shows promising results even for larger defects. But for a final decision about this therapy the present sample size was too small. There is a need for further long-term investigation with a larger number of patients.


The ultrastructure of signet-ring cell non-Hodgkin's lymphoma.
New ultrastructural findings are reported from two lymphomas of vacuolar signet-ring cell morphology (SR+), one of B cell and one of T cell lineage. When these lymphomas were compared ultrastructurally a difference in the relationship of the endoplasmic reticulum (ER) to the vacuole was noted, although the fine structure of the vacuoles themselves was similar and they were interpreted as giant multivesicular bodies (mvbs). Smooth ER was found near the vacuoles in both cases. Dark mvbs with a complex, reticulate form are emphasised as readily identified but hitherto unreported cell components in these tumours. A further B cell lymphoma of centroblastic/centrocytic type which was SR- was found to be rich in mvbs and may be a transitional form between SR- and SR+ lymphomas. In addition, the occurrence of mvbs has been studied quantitatively in a number of other lymphomas and in B and T lymphocytes in reactive nodes. Although increased numbers of mvbs were found in neoplastic compared with reactive lymphocytes, and in T compared with B cell lymphomas, these differences were not statistically significant. The possible roles of endoplasmic reticulum and mvbs in the generation of SR+ change are discussed.


Extracellular vesicles from human pancreatic islets suppress human islet amyloid polypeptide amyloid formation.
Extracellular vesicles (EVs) are small vesicles released by cells to aid cell-cell communication and tissue homeostasis. Human islet amyloid polypeptide (IAPP) is the major component of amyloid deposits found in pancreatic islets of patients with type 2 diabetes (T2D). IAPP is secreted in conjunction with insulin from pancreatic β cells to regulate glucose metabolism. Here, using a combination of analytical and biophysical methods in vitro, we tested whether EVs isolated from pancreatic islets of healthy patients and patients with T2D modulate IAPP amyloid formation. We discovered that pancreatic EVs from healthy patients reduce IAPP amyloid formation by peptide scavenging, but T2D pancreatic and human serum EVs have no effect. In accordance with these differential effects, the insulin:C-peptide ratio and lipid composition differ between EVs from healthy pancreas and EVs from T2D pancreas and serum. It appears that healthy pancreatic EVs limit IAPP amyloid formation via direct binding as a tissue-specific control mechanism.


Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions.
To investigate whether the abnormal expression of matrix metalloproteinases (MMPs) 3, 9, and 13 and ADAMTS-4 by human osteoarthritic (OA) chondrocytes is associated with epigenetic "unsilencing." Cartilage was obtained from the femoral heads of 16 patients with OA and 10 control patients with femoral neck fracture. Chondrocytes with abnormal enzyme expression were immunolocalized. DNA was extracted, and the methylation status of the promoter regions of MMPs 3, 9, and 13 and ADAMTS-4 was analyzed with methylation-sensitive restriction enzymes, followed by polymerase chain reaction amplification. Very few chondrocytes from control cartilage expressed the degrading enzymes, whereas all clonal chondrocytes from late-stage OA cartilage were immunopositive. The overall percentage of non-methylated sites was increased in OA patients (48.6%) compared with controls (20.1%): 20% versus 4% for MMP-13, 81% versus 47% for MMP-9, 57% versus 30% for MMP-3, and 48% versus 0% for ADAMTS-4. Not all CpG sites were equally susceptible to loss of methylation. Some sites were uniformly methylated, whereas in others, methylation was generally absent. For each enzyme, there was 1 specific CpG site where the demethylation in OA patients was significantly higher than that in controls: at -110 for MMP-13, -36 for MMP-9, -635 for MMP-3, and -753 for ADAMTS-4. This study provides the first evidence that altered synthesis of cartilage-degrading enzymes by late-stage OA chondrocytes may have resulted from epigenetic changes in the methylation status of CpG sites in the promoter regions of these enzymes. These changes, which are clonally transmitted to daughter cells, may contribute to the development of OA.


Eating disorders among fashion models: a systematic review of the literature.
In the light of recent concerns regarding the eating disorders among fashion models and professional regulations of fashion model occupation, an examination of the scientific evidence on this issue is necessary. The article reviews findings on the prevalence of eating disorders and body image concerns among professional fashion models. A systematic literature search was conducted using ProQUEST, EBSCO, PsycINFO, SCOPUS, and Gale Canage electronic databases. A very low number of studies conducted on fashion models and eating disorders resulted between 1980 and 2015, with seven articles included in this review. Overall, results of these studies do not indicate a higher prevalence of eating disorders among fashion models compared to non-models. Fashion models have a positive body image and generally do not report more dysfunctional eating behaviors than controls. However, fashion models are on average slightly underweight with significantly lower BMI than controls, and give higher importance to appearance and thin body shape, and thus have a higher prevalence of partial-syndrome eating disorders than controls. Despite public concerns, research on eating disorders among professional fashion models is extremely scarce and results cannot be generalized to all models. The existing research fails to clarify the matter of eating disorders among fashion models and given the small number of studies, further research is needed.


Effect of verbal and nonverbal short-term memory coding with normal and retarded children.
20 retarded children (CA 11.7 yr.), matched with 20 normal ones, were assigned to verbal or nonverbal stimulus conditions. Pairs of 8-point random shapes were shown as styrofoam objects or drawings. d' measures for adjacent positions showed better recall for verbal coding and three-dimensional stimuli. Serial position effects were noted. Coding and dimensionality interacted.


Dextran receptors as immunogens in caries prophylaxis.
1) Immunization of rats with dextran receptors appears to confer resistance to development of caries. 2) A significant negative correlation between antiserum titers and caries scores is observed in immunized rats. 3) Antiserum specific for dextran receptors does not inhibit in vitro adherence of live bacteria in sucrose supplemented media. 4) Free receptors can bind to dextran, thereby inhibiting its ability to induce bacterial agglutination.


Exploring the Superior Anchoring Performance of the Two-Dimensional Nanosheets B2C4P2 and B3C2P3 for Lithium-Sulfur Batteries.
Potential anchoring materials in lithium-sulfur batteries help overcome the shuttle effect and achieve long-term cycling stability and high-rate efficiency. The present study investigates the two-dimensional nanosheets B2C4P2 and B3C2P3 by employing density functional theory calculations for their promise as anchoring materials. The nanosheets B2C4P2 and B3C2P3 bind polysulfides with adsorption energies in the range from -2.22 to -0.75 and -2.43 to -0.74 eV, respectively. A significant charge transfer occurs from the polysulfides, varying from -0.74 to -0.02e and -0.55 to -0.02e for B2C4P2 and B3C2P3, respectively. Upon anchoring the polysulfides, the band gap of B3C2P3 reduces, leading to enhanced electrical conductivity of the sulfur cathode. Finally, the calculated barrier energies of B2C4P2 and B3C2P3 for Li2S indicate fast diffusion of Li when recharged. These enthralling characteristics propose that the nanosheets B2C4P2 and B3C2P3 could reduce the shuttle effect in Li-S batteries and significantly improve their cycle performance, suggesting their promise as anchoring materials.


Histochemical and Molecular Quantification of Arbuscular Mycorrhiza Symbiosis.
Arbuscular mycorrhizae (AM) are one of the most widespread and studied plant associations with beneficial microorganisms. Indeed, more than 80% of land plants, including most agricultural and horticultural crop species, are able to establish this mutualistic symbiosis with AM fungi. Through this association the fungus helps the plant in the acquisition of water and mineral nutrients, especially under stress conditions. AM symbiosis affects other ecologically and economically important traits such as plant architecture, flowering, and fruit quality but also tolerance against biotic and abiotic stresses. As a consequence, AM fungi have a great potential as biofertilizers and bioprotection agents in sustainable agriculture. However, in order to take advantage of all these benefits, a good and functional symbiosis is required. Here we present methods for reliable quantification of colonization levels which should be useful not only for research but also from the agronomic point of view.


The Brazilian market of herbal medicinal products and the impacts of the new legislation on traditional medicines.
the herbal medicinal products (HMP) market is expanding in the world, an expansion that has not occurred in Brazil when considering the number of licensed products. Despite being a megadiverse country, the number of HMP licensed in Brazil is small, and the number of HMP obtained from native species is even smaller. A new legislation for herbal products licensing, which divides the products into two categories, Herbal Medicine (HM) and Traditional Herbal Product (THP) was launched in Brazil focusing on traditional use, as well as a law regulating the use of biodiversity and traditional knowledge. to evaluate the situation of HMP licensed in Brazil and to make a comparison with the data obtained in 2008 and 2011, discussing the evolution of the licensed products and the possible impacts of the new legislation. a survey was carried out in the Brazilian Health Regulatory Agency (Anvisa) database to verify the HMP licensed in Brazil in September 2016. The data obtained were compared with two surveys previously published. There are 332 single, and 27 combined HM, totaling 359 HM licensed in Brazil. There is no THP notified in Anvisa's system yet. There are 214 HM classified as nonprescription (OTC), while 145 are sold under prescription, one of them with prescription retention. There are 101 plant species licensed as active in HM in Brazil, 39 of which are native, adapted or cultivated. The most licensed plant species is Mikania glomerata Spreng., with 25 HM licensed. The article includes tables with plant species that have derivatives licensed as simple and combined HM, their therapeutic classification, the native plant species indication and the distribution of the companies by Brazilian regions. There are few licensed HM in Brazil, and this number has been decreasing in recent years. It is expected that the data obtained, together with the changes promoted in sanitary and environmental rules, will help to develop and regulate HMP chain in Brazil.


Clinical implications of skeletal muscle blood-oxygenation-level-dependent (BOLD) MRI.
Blood-oxygenation-level-dependent (BOLD) contrast in magnetic resonance (MR) imaging of skeletal muscle mainly depends on changes of oxygen saturation in the microcirculation. In recent years, an increasing number of studies have evaluated the clinical relevance of skeletal muscle BOLD MR imaging in vascular diseases, such as peripheral arterial occlusive disease, diabetes mellitus, and chronic compartment syndrome. BOLD imaging combines the advantages of MR imaging, i.e., high spatial resolution, no exposure to ionizing radiation, with functional information of local microvascular perfusion. Due to intrinsic contrast provoked via changes in hemoglobin oxygen saturation, it is a safe and easy applicable procedure on standard whole-body MR devices. Therefore, BOLD MR imaging of skeletal muscle is a potential new diagnostic tool in the clinical evaluation of vascular, inflammatory, and muscular pathologies. Our review focuses on the current evidence concerning the use of BOLD MR imaging of skeletal muscle under pathological conditions and highlights ways for future clinical and scientific applications.


Recirculating packed-bed biofilm photobioreactor combined with membrane ultrafiltration as advanced wastewater treatment.
Packed-bed biofilm photobioreactor combined with ultrafiltration membrane was investigated for intensifying the process for secondary wastewater effluent treatment. Cylindrical glass carriers were used as supporting material for the microalgal-bacterial biofilm, which developed from indigenous microbial consortium. Glass carriers allowed adequate growth of the biofilm with limited suspended biomass. Stable operation was achieved after a start-up period of 1000 h, where supernatant biopolymer clusters were minimized and complete nitrification was observed. After that time, biomass productivity was 54 ± 18 mg·L-1·day-1. Green microalgae Tetradesmus obliquus and several strains of heterotrophic nitrification-aerobic denitrification bacteria and fungi were identified. Combined process exhibited COD, nitrogen and phosphorus removal rates of 56 ± 5%, 12 ± 2% and 20 ± 6%, respectively. Membrane fouling was mainly caused by biofilm formation, which was not effectively mitigated by air-scouring aided backwashing.


Maternal diabetes affects rat offspring retinal structure and function: Sex-specific vulnerabilities at infancy.
Maternal diabetes negatively impacts the offspring's brain, but little is known about its effects on the retina, which is also part of the central nervous system. We hypothesized that maternal diabetes adversely influences offspring retina development leading to structural and functional deficits. Retinal structure and function were evaluated at infancy, by optical coherence tomography and electroretinography, in male and female offspring of control, diabetic and diabetic-treated with insulin Wistar rats. Maternal diabetes induced a delay in male and female offspring eye-opening, while insulin treatment expedited it. Structural analysis showed that maternal diabetes decreased the thickness of the inner and outer segment layer of photoreceptors in male offspring. Electroretinography also revealed that maternal diabetes decreased the amplitude of scotopic b-wave and flicker response in males, suggesting bipolar cells and cone photoreceptor dysfunction, an effect not observed in females. Conversely, maternal diabetes decreased cone arrestin protein levels in female retinas, while not affecting cone photoreceptor number. Dam insulin therapy was efficient in preventing the offspring photoreceptor changes. Our results suggest that photoreceptors are affected by maternal diabetes, which may account for visual impairments at infancy. Notably, both male and female offspring presented specific vulnerabilities to hyperglycemia in this sensitive period of development.


N-3 and N-6 phosphoglyceride fatty acids in relation to in vitro erythrocyte haemolysis induced by hydrogen peroxide in captive common marmosets (Callithrix jacchus).
1. Hydrogen peroxide-induced haemolysis (HPIH) was studied in the red blood cells of the common marmoset monkey (Callithrix jacchus) in relation to the composition of the membrane fatty acids. HPIH (%) was surprisingly high (mean 41% +/- 34; median 33.4%) and significantly different (P less than 0.001) from the corresponding value in healthy human subjects (mean 0.98% +/- 0.6; median 1.3%). 2. It was negatively correlated with 18:2n-6 (r = -0.76, P less than 0.001), 18:2n-6/20:4n-6 (r = -0.70, P less than 0.005) and 18:2n-6/22:6n-3 (r = -0.44, P less than 0.025) in the ethanolamine phosphoglycerides of the erythrocytes. 3. A shift in the n-6/n-3 balance in favour of the n-3 in the fatty acid composition of the membrane may have predisposed the red blood cells to haemolysis. 4. An increase in 22:6n-3, and a decrease of 20:4n-6 and 18:2n-6, may have been the result of feeding a diet containing fish products rich in long chain n-3 fatty acids.


Genetics, epigenetics, and the environment: switching, buffering, releasing.
Increasing evidence suggests that the interactions between genes and environment might play a critical role in the pathogenesis of complex diseases, such as asthma, that exhibit a heritable component but do not follow Mendel's laws. Gene-environment interactions are extremely complex and not linear, such that the same genetic variants might be associated with opposite phenotypes in different environments. This is particularly evident for innate immunity genes, which operate at the interface between the immune system and the pathogen world. This article examines gene-environment interactions by using CD14 as a model and argues that the conflicting results of epidemiologic studies on CD14*C-159T result from differences in environmental conditions essential to modulate CD14 gene expression. Furthermore, on the basis of how rapidly environmental changes have affected the incidence of immune diseases, I argue that a full understanding of gene-environment interactions requires that epigenetic as well as classical genetic mechanisms be taken into account. Recent data about the effect of diet on gene methylation and the release of hidden genetic variation by impairment of heat shock protein 90-mediated buffering systems offer eloquent examples of how epigenetic mechanisms might affect gene-environment interactions.


Serum prostatic acid phosphatase determination in prostatic diseases: a critical comparison of an enzymatic and a radioimmunologic assay.
A prospective study comparing a new radioimmunologic and a classical enzymatic assay for prostatic acid phosphatase was done to evaluate their respective roles in patients with prostatic diseases. We studied 50 patients with cancer of the prostate, 101 with benign prostatic hypertrophy and 17 with prostatitis as well as patients with nonprostatic malignancy, and various hematological and bone diseases. The results showed a low incidence of elevated values in patients with early cancer of the prostate and a high incidence of false positive values with the radioimmunoassay in patients with benign prostatic diseases, especially prostatitis. These data suggest that tests for serum prostatic acid phosphatase levels remain disappointing in the assessment of prostatic disease regardless of the technique used.


Fevers and the social costs of acute infection in wild vervet monkeys.
Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.


Translational aspects in targeting the stromal tumour microenvironment: from bench to bedside.
Solid tumours comprise, not only malignant cells but also a variety of stromal cells and extracellular matrix proteins. These components interact via an array of signalling pathways to create an adaptable network that may act to promote or suppress cancer progression. To date, the majority of anti-tumour chemotherapeutic agents have principally sought to target the cancer cell. Consequently, resistance develops because of clonal evolution, as a result of selection pressure during tumour expansion. The concept of activating or inhibiting other cell types within the tumour microenvironment is relatively novel and has the advantage of targeting cells which are genetically stable and less likely to develop resistance. This review outlines key players in the stromal tumour microenvironment and discusses potential targeting strategies that may offer therapeutic benefit.


Postoperative complications after chemoradiation for advanced head and neck cancer.
To compare the rate of postoperative complications of patients with advanced head and neck cancer treated with the chemoradiation protocol "RADPLAT" with that of a similar cohort of patients treated with primary surgery. We retrospectively analyzed 50 patients treated with RADPLAT and 50 patients treated with primary surgery. The rates of complications for local wound problems were 54% and 42%, respectively, for the RADPLAT cohort and the primary surgery cohort. However, the rate of local complications for the subset of RADPLAT patients undergoing clean-contaminated surgery was 69% (p =.305). The rates of complications for medical (systemic) problems were 10% and 12%, respectively, for RADPLAT versus primary surgery patients. There was no significant difference in hospitalization time between the groups. Among patients with advanced head and neck cancer, surgical complications are high but not significantly different between patients undergoing the chemoradiation protocol "RADPLAT" and those undergoing primary surgery.


Evaluation of the Effects of Administering Ultradiluted Avena sativa and Echinacea angustifolia on the Hematological Parameters of Magellanic penguins (Spheniscus magellanicus) during the Reproductive Period.
Penguins are seabirds that manifest physiological and immunological alterations during the reproductive season. The objectives of this study were to evaluate the laboratory parameters of male and female Magellanic penguins and to determine the penguins' hematological response to homeopathic medicines during that reproductive period. Penguins (N = 18), kept under human care in a zoological park setting, were evaluated during the reproductive period and were divided randomly into two groups: a group subjected to treatment with Echinacea angustifolia 6cH and Avena sativa 6cH (N = 8; four breeding couples), and a placebo control group (N = 10; five breeding couples). The investigators were blinded to treatment allocation. Two-way ANOVA was performed to determine whether the experimental group (control or verum) and the sex of the animal had any significant effect on the variation of each hematological parameter between the samples. One-way ANOVA was performed on hematological parameters for which the sex did not present a significant effect. The significance level was p ≤0.05. Significant effects were seen regarding the following: mean corpuscular volume (MCV), in which the verum group showed an increase (29.78 ± 52.95 fL) while the control group showed stability/reduction (-3.08 ± 46.36 fL) (p = 0.049); proportion of heterophils, in which the verum group showed a less marked increase (8.38 ± 12.53%) than that of the control group (18.00 ± 9.37%) (p = 0.010); lymphocyte concentration, in which the verum group showed less marked reduction (-4.39 ± 2.21 × 109 cells/L) than that of the control group (-1.56 ± 2.76 × 109 cells/L) (p = 0.001); and proportion of lymphocytes, in which the verum group showed a less marked reduction (-6.75 ± 10.35%) than that of the control group (-17.3 ± 8.73%) (p = 0.002). Comparison of samples collected before and during the reproductive period showed that, regardless of group allocation, there were differences in the effects on MCV, heterophils and lymphocytes. Treatment with Echinacea angustifolia and Avena sativa resulted in maintenance of lymphocyte levels in Magellanic penguins during the breeding period, thus aiding these birds' immunity.


Association between anxiety disorders and a functional polymorphism in the serotonin transporter gene.
Recently, individuals with the short form of the serotonin transporter were found to be associated with neurotic characteristics. An association study on this polymorphism was performed in anxiety disorder patients and control subjects. The short form allele frequency in patients tended to be higher than that in control subjects (81.7 vs. 74.5%). Although it is difficult to ascribe significance to these 'tendencies', these data may suggest that variation of this functional polymorphism makes some contribution to anxiety disorders.


Principles of reproducible metabolite profiling of enriched lymphocytes in tumors and ascites from human ovarian cancer.
Identifying metabolites and delineating their immune-regulatory contribution in the tumor microenvironment is an area of intense study. Interrogating metabolites and metabolic networks among immune cell subsets and host cells from resected tissues and fluids of human patients presents a major challenge, owing to the specialized handling of samples for downstream metabolomics. To address this, we first outline the importance of collaborating with a biobank for coordinating and streamlining workflow for point of care, sample collection, processing and cryopreservation. After specimen collection, we describe our 60-min rapid bead-based cellular enrichment method that supports metabolite analysis between T cells and tumor cells by mass spectrometry. We also describe how the metabolic data can be complemented with metabolic profiling by flow cytometry. This protocol can serve as a foundation for interrogating the metabolism of cell subsets from primary human ovarian cancer.


Feasibility of Telehealth Occupational Therapy for Behavioral Symptoms of Adults With Dementia: Randomized Controlled Trial.
Supporting community residency of adults with Alzheimer's disease (AD) is a critical public health initiative. Occupational therapy can contribute to this goal. To assess the feasibility of a novel telehealth intervention to support occupational engagement in community-residing people with AD. Single-blind, three-arm, parallel, randomized controlled trial. Occupational therapy delivered through telehealth in participants' homes. People with AD who reside in the community with behavioral symptoms and their care partners (dyads). (1) HARMONY (Helping older Adults cReate & Manage OccupatioNs successfully), a telehealth intervention that applies principles of individualized guided discovery with environmental cueing for caregivers of persons with AD to promote activity participation and manage behavioral symptoms; (2) standardized training regarding the use of a sensory-based approach in dementia care; and (3) a control, including home safety education and weekly monitoring of behaviors. Feasibility was assessed as the primary outcome measured by completion of at least 75% of the telehealth sessions. Secondary outcomes included change in functional activity performance and neuropsychiatric behavioral symptoms. Twenty-eight dyads participated. The intervention was feasible, with high adherence to weekly visits (M number of visits = 5.4 for HARMONY, 4.9 for standardized training, and 4.6 for control), with high participant retention in the intervention arms. HARMONY demonstrated promise in improving patient performance and behavioral symptoms. HARMONY is feasibly delivered through telehealth service and has a positive effect on occupational performance and behavioral symptoms of AD. Additional studies are needed to explore effectiveness in a broader population. What This Article Adds: Use of HARMONY for community-residing adults with AD is feasible and has promise for improving functional activity performance and behavioral symptoms, as well as caregiver satisfaction.


War on Two Fronts: Experience of Children with Cancer and Their Family During COVID-19 Pandemic in Iran.
The COVID-19 pandemic affects all age groups and presents differently in children from adults. Children who contract the virus while suffering from cancer may face unique health challenges than their counterparts. This study aimed to investigate the perspectives of children with cancer and their family in this era of the COVID-19 pandemic. In this qualitative study, a total of 21 participants were interviewed. They include five children, thirteen mothers, a father and three pediatric oncology nurses. The study setting was a Pediatric Hospital in Tehran, Iran. Three main themes were identified through thematic analysis. 1) Swinging on the path of fear to adaptation, 2) Left-alone at emotional distances, 3) Care system confusion, and decreased quality of care. The COVID-19 pandemic has burdened children living with cancer and their families in varying ways. Their experiences show a new insight on how to improve their quality of life during these difficult times.


[Effect of destruction of the amygdaloid complex on the cardiac and motor components of a conditioned defense reaction].
The effect of bilateral ablation of the amygdala complex basolateral part on heart and motor components of conditioned defensive reaction was studied in chronic experiments on rats. After 10 presentations of the tone during habituation procedure the elaboration of conditioned reaction in operated and control animals was achieved in one session (10 pairings of the tone with electrical pain stimulation in a minute). The analysis of the changes in the heart rate of amygdalectomized rats immediately after the elaboration revealed a shorter time of retention of the heart rate tachycardiac changes elicited by aversive stimulation. In tests one hour and 24 hours after the elaboration, the operated animals showed no conditioned bradycardiac reaction to the tone. This fact suggests a severe impairment of the conditioned emotional reaction of fear. The absence of the emotional component of the conditioned reaction seems to result in the disturbance of reproduction of its motor component.


A comparative study between high ligation of the inter-sphincteric fistula tract via lateral Approach Versus Fistulotomy and primary sphincteroplasty in High Trans-Sphincteric Fistula-in-Ano: a randomized clinical trial.
Trans-sphincteric fistula management is very challenging and everyday new techniques are introduced to reach the safest and the most effective technique. In this study two of the most effective techniques are compared based on their post-operative outcomes. To compare the efficacy of high ligation of the inter-sphincteric fistula tract by lateral approach (modified LIFT) and Fistulotomy and primary sphincteroplasty (FIPS) in the management of high trans-sphincteric fistula regarding their post-operative outcomes in the form of post-operative pain, time of wound healing in weeks, wound infection, incontinence and recurrence within one year. The current study is single-blind, prospective, randomized, controlled, single-center trial conducted from June 2020 to June 2022 in the colorectal surgical unit of Ain Shams University Hospitals, which included 80 patients presented with high trans-sphincteric perianal fistula 55 (68.75%) males and 25 (31.25%) including a one-year follow-up postoperative. There were 80 patients in our study 40 patients in each group. The mean age of group (I) is 46.65 with standard deviation 6.6. while, in group (II) the mean age is 45.85 with standard deviation 6.07 (p = 0.576). From the included 80 patients 55(68.7%) were males and 25 (31.25%) were females (p = 0.469). Regarding, postoperative wound infection occurred in 2(5%) Patients in group (I) and 7(17.5%) patients in group (II) (p = 0.154). There were no cases of incontinence in group I. However, there were 6(15%) cases of incontinence to gases only scored by Wexner score 3/20 in group II (p = 0.026) and its significant difference between the two techniques. Postoperative pain was assessed for one week duration by the visual analogue score (VAS) from 0 to 10 in which, zero is the least and 10 is the maximum. In group (I) 18(45%) patients scored their pain mild from 1 to 3, 20(50%) patients scored their pain moderate from 4 to 6 and 2(5%) patients scored severe pain from 7 to 9. While, in group (II) 14(35%) patients scored their pain mild from 1 to 3, 22(55%) patients their pain moderate from 4 to 6 and 4(10%) patients scored their pain severe from 7 to 9 (p = 0.275). Recurrence in one-year follow-up occurred in 13(32.5%) patients in group (I) about 7 patients had recurrence in the form of inter-sphincteric fistula and 6 patients in the form of trans-sphincteric fistula. While, in group II recurrence occurred in 1 (2.5%) patient in the form of subcutaneous fistula at the healing site (p = 0.001). Fistulotomy and primary sphincteroplasty is an effective and preferred technique for the trans-sphincteric fistula repair with high statistically significant lower incidence of recurrence in one-year follow-up as compared to modified LIFT technique. Although, there is higher incidence regarding incontinence to gases only post-operative. This work recommends fistulotomy and primary sphincter reconstruction procedure in high trans-sphincteric perianal fistulas to be more popular, to be implemented as a corner stone procedure along various and classic operations for such cases as it's easy, feasible.


Characterizing the interplay between multiple levels of organization within bacterial sigma factor regulatory networks.
Bacteria contain multiple sigma factors, each targeting diverse, but often overlapping sets of promoters, thereby forming a complex network. The layout and deployment of such a sigma factor network directly impacts global transcriptional regulation and ultimately dictates the phenotype. Here we integrate multi-omic data sets to determine the topology, the operational, and functional states of the sigma factor network in Geobacter sulfurreducens, revealing a unique network topology of interacting sigma factors. Analysis of the operational state of the sigma factor network shows a highly modular structure with σ(N) being the major regulator of energy metabolism. Surprisingly, the functional state of the network during the two most divergent growth conditions is nearly static, with sigma factor binding profiles almost invariant to environmental stimuli. This first comprehensive elucidation of the interplay between different levels of the sigma factor network organization is fundamental to characterize transcriptional regulatory mechanisms in bacteria.


Efficacy and safety of probiotics and synbiotics for functional constipation in children: A systematic review and meta-analysis of randomized clinical trials.
We aimed to evaluate the efficacy and safety of probiotics and synbiotics in childhood functional constipation. PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) were searched up to June 2023. Randomized controlled trials involving children diagnosed with FC with Rome III/IV criteria were included. Treatment success, defecation frequency, stool consistency, painful defecation, fecal incontinence, and adverse events were assessed as outcomes. Odds ratios (ORs) and standard mean difference (SMD) with 95% confidence intervals (CIs) were calculated for dichotomous and continuous variables as appropriate. Cochrane risk-of-bias tool version 2 assessed the risk of bias. Seventeen RCTs with 1504 patients were included. Compared to placebo, probiotics significantly improved defecation frequency (SMD 0.40, 95% CI 0.10 to 0.70, I2 = 0%) and fecal incontinence (OR 0.53, 95% CI 0.29 to 0.96, I2 = 0%). However, it did not significantly improve treatment success, painful defecation, and abdominal pain. Probiotics, as add-on therapy, failed to yield a significant difference in treatment success (OR 0.82, 95% CI 0.15 to 4.48, I2 = 52%), defecation frequency (SMD 0.13, 95% CI -0.13 to 0.39, I2 = 0%), defecation consistency (SMD -0.01, 95% CI -0.40 to 0.38, I2 = 1%), fecal incontinence (OR 0.95, 95% CI 0.48 to 1.90, I2 = 0%), and abdominal pain (OR, 0.60, 95% CI 0.24 to 1.53, I2 = 0%) versus laxatives monotherapy. Synbiotics plus laxatives showed no significant effect on defecation frequency (SMD -0.57; 95% CI -1.29 to 0.14, I2 = 74%) and painful defecation (OR, 3.39; 95% CI 0.74 to 15.55, I2 = 0%) versus laxatives alone. Current evidence did not advocate using probiotics and synbiotics in treating functional constipation in children. At this time, the effects of strain-specific probiotics, probiotics mixtures, and the optimal doses and treatment durations of the probiotics and synbiotics were unclear. Additional rigorous evidence is required to evaluate and establish the effectiveness and safety of probiotics and synbiotics for childhood functional constipation. CRD42020195869.


Laparoscopic repositioning of an adjustable silicone gastric band for pouch dilatation and stoma obstruction.
Pouch dilatation with stoma obstruction is a well-known late complication after adjustable gastric banding operations for morbid obesity. Surgical treatment of this problem usually results in removal of the band, with or without replacement by another, or in repositioning of the band via laparotomy. We present the case of a patient with late pouch dilatation and stoma obstruction after placement of a Laparoscopic Adjustable Gastric Banding system (LAGB-Bioenterics) and in whom the adjustable band was laparoscopically opened, disconnected from the access port, and repositioned more proximally on the stomach. The postoperative course was uneventful. A postoperative radiographic contrast examination showed a correct repositioning of the band. The case demonstrates that the LAGB can be successfully opened and repositioned by a minimal invasive procedure. This is the first time to our knowledge that such a procedure has been reported.


Current Role of Radiation Therapy in the Management of Malignant Central Nervous System Tumors.
The 2016 World Health Organization classification of central nervous system (CNS) tumors underwent significant restructuring and for the first time gliomas are classified according to both molecular and histologic parameters which guides glioma management. Radiation for intermediate-risk meningiomas improves the progression-free survival from historical controls, and studies are ongoing for atypical meningiomas. For brain metastases, use of stereotactic radiosurgery for a higher number of lesions has become clinical practice. Additionally, hippocampal-sparing whole brain radiation shows promise in preserving neuro-cognitive function. This article summarizes the evolving role of radiation therapy in the management of malignant CNS neoplasms.


Development of highly-sensitive microbial biosensors by mutation of the nahR regulatory gene.
NahR, a transcriptional regulator for naphthalene degradation in response to salicylate, is a central element in the microbial biosensor for detection of naphthalene and salicylate. To maximize the sensitivity of the biosensor, we have chosen a rational design of highly-sensitive microbial biosensors by introducing site directed mutagenesis to nahR gene. Eight single mutants (N169A, N169C, N169K, N169S, R248H, R248M, R248Q, and R248Y) were made at residues 169 and 248 known as the central inducer-recognition and the C-terminal multimerization domain. The effects of these mutations were examined by monitoring expression of a firefly luciferase (luc) reporter gene under the control of NahR. We found that all mutants at residues 248 and N169C show increased sensitivity (maximum ∼50-fold) compared to wild type, respectively. R248M shows response even at toxic concentration, 5mM. The results show the feasibility and potential versatility of mutational approach for the development of the highly-sensitive microbial biosensors.


Methionine metabolism in apple tissue.
A metabolic intermediate isolated from apple tissue fed either methionine or 5'-methylthioadenosine has been tentatively identified as a methionine-pyridoxal Schiff base. The formation of this compound is discussed in relation to ethylene biosynthesis.


Influence of posture on pharmacokinetics.
Body position may influence physiological characteristics, such as perfusion, gastrointestinal function and plasma volume. These characteristics may interact with key factors determining the pharmacokinetics of drugs (dissolution, absorption, distribution, metabolism, excretion). Based on a systematic literature search, current data on the effect of posture on physiological characteristics and/or pharmacokinetics are summarized, and the relevance of possible effects, such as those presenting in clinical practice and clinical pharmacokinetic studies, is assessed. Postures which favour rapid gastric emptying (sitting, standing, recumbent right) accelerate the absorption of orally administered drugs. Consequently, these postures favour a shorter time to reach peak plasma drug concentration (t(max)) and a higher maximum plasma drug concentration (C(max)) and--in the case of transient saturation of first-pass metabolism--total exposure (area under the concentration-time curve, AUC) in comparison to recumbent left and supine positions (e.g. nifedipine: AUC 30 and 38% higher in standing and right lateral position vs. left lateral position; C(max) 149 and 80% higher, respectively). The magnitude of these postural effects depends strongly on the nature and amount of liquids and food ingested before drug administration and is most pronounced in the fasting state and after administration with a nonnutrient liquid. Changes in splanchnic-hepatic blood flow (e.g. reduction of estimated hepatic perfusion by 37% in standing vs. supine position) may substantially affect the metabolism of orally administered drugs, especially of those with a high/saturable first-pass metabolism. For highly protein-bound drugs (e.g. phenytoin, imipramine), the total plasma concentration has been found to be approximately 10% higher in standing than lying subjects due to changes in plasma volume. Positioning of a patient may be an effective method of enhancing or retarding absorption of some drugs in appropriate clinical situations (e.g. toxic ingestions, bedridden patients). In clinical pharmacokinetic trials, such as bioequivalence studies, defining and maintaining posture precisely is a useful approach for reducing within- and between-subject variability.


A moving liver phantom in an anthropomorphic thorax for SPECT MP imaging.
Cranio-caudal respiratory motion and liver activity cause a variety of complex myocardial perfusion (MP) artifacts, especially in the inferior myocardial wall, that may also mask cardiac defects. To assess and characterise such artifacts, an anthropomorphic thorax with moving thoracic phantoms can be utilised in SPECT MP imaging. In this study, a liver phantom was developed and anatomically added into an anthropomorphic phantom that also encloses an ECG beating cardiac phantom and breathing lungs' phantom. A cranio-caudal respiratory motion was also developed for the liver phantom and it was synchronised with the corresponding ones of the other thoracic phantoms. This continuous motion was further divided into isochronous dynamic respiratory phases, from end-exhalation to end-inspiration, to perform SPECT acquisitions in different respiratory phases. The new motions' parameters and settings were measured by mechanical means and also validated in a clinical environment by acquiring CT images and by using two imaging software packages. To demonstrate the new imaging capabilities of the phantom assembly, SPECT/CT MP acquisitions were performed and compared to previous phantom and patients studies. All thoracic phantoms can precisely perform physiological motions within the anthropomorphic thorax. The new capabilities of the phantom assembly allow to perform SPECT/CT MP acquisitions for different cardiac-liver activity ratios and cardiac-liver proximities in supine and, for first time, in prone position. Thus, MP artifacts can be characterised and motion correction can be performed due to these new capabilities. The impact of artifacts and motion correction on defect detection can be also investigated.


Quercetin reduces tendon adhesion in rat through suppression of oxidative stress.
Tendon adhesion is one of the most common clinical problems, which poses a considerable challenge to orthopedics doctors. Quercetin (QUE) as a popular drug at present, it has various biological functions, including anti-inflammatory, anti-ischemic, anti-peroxidation, and antioxidant. The purpose of this study was to investigate the effect of quercetin on tendon adhesion and whether quercetin can inhibit oxidative stress. Thirty-six rats were randomly divided into three groups, including control group, low QUE (50 mg/kg/day) group, and high QUE (100 mg/kg/day) group. After 1 week, the levels of SOD, MDA and GPx were measured. The degree of tendon adhesion was assessed by macroscopic evaluation and histological evaluation. After 4 weeks. Besides, the pharmacological toxicity of quercetin to main organs were evaluated by histological analysis. The extent of superoxide dismutase (SOD) and glutathione peroxidase (GPx) of tendon tissue in high QUE group was significantly higher than those of low QUE group and control group. And the extent of malondialdehyde (MDA) of tendon tissue in high QUE group was significantly lower than that of low QUE group and control group. By macroscopic evaluation and histological analysis, the extent of tendon adhesion in high QUE group was lower than low QUE group and control group. However, there were no significant changes of the major organs through histological analysis. Quercetin may be a good and safe strategy in preventing tendon adhesion. But further clinical research is needed before its recommendation in the prevention and treatment of tendon adhesion.


Immobilization and characterization of hemoglobin on modified sporopollenin surfaces.
Hemoglobin was covalently immobilized onto modified sporopollenin surface with different functional groups by chemical reactions to enhance binding ability of protein. In this study, the influence of various silane linker molecules on the capacity of protein binding was studied. For this purpose, activated sporopollenin was modified by 3-aminopropyltriethoxysilane (APTS), 3-chloropropyltrimethoxysilane (CPTS) and (3-glycidyloxypropyl)trimethoxysilane (GPTS). Hemoglobin (Hb) was immobilized on modified sporopollenin surfaces in phosphate buffer saline solution (PBS, pH 7.4) at 4°C. Results showed that GPTS modified sporopollenin surfaces resulted in the highest binding capacity for Hb. Micro porosity of samples was observed through scanning electron microscopy (SEM) and thermal behavior of the samples were studied with thermogravimetric analysis (TGA) within a temperature range: 25-900°C. TGA studies demonstrated the advantages of silane modification for high temperature applications and illustrated differences of the structures due to the different tail groups.


Refining clinical judgment of treatment outcome in obsessive-compulsive disorder.
This research aimed to provide clinicians and investigators with optimal treatment outcome criteria for accurately predicting response and remission in both research studies and clinical practice. Data from 153 adult OCD outpatients (ages 18-79) who had participated in a treatment outcome study were examined. Signal detection analysis was conducted to compare levels of Yale-Brown Obsessive Compulsive Scale (Y-BOCS) symptom percent reductions and post treatment absolute scores with Clinical Global Impression (CGI) ratings of symptom improvement and severity. Optimal cutoff criteria were based on sensitivity, specificity and efficiency and were assessed via the Quality Receiver Operating Characteristic curve. A Y-BOCS reduction of 45% was observed to be the most efficient for predicting response in research trials, whereas a reduction of 35% may be optimal for clinical use. A 55% Y-BOCS reduction was determined to be the optimal cutoff for predicting remission in both clinical and research settings. A Y-BOCS absolute raw score of 12 or less was optimal for predicting remission in a clinical setting and a raw score of 14 or below was most favorable in research trials. This research provides the first empirical contrast of optimal outcome criteria in OCD based on differing ideals of both research and practice.


Leukocyte counting from a small amount of whole blood using a size-controlled microcavity array.
Absolute counting of total leukocytes or specific subsets within small amounts of whole blood is difficult due to a lack of techniques that enable separation of all leukocytes from limited amounts of whole blood. In this study, a microfluidic device equipped with a size-controlled microcavity array for highly efficient separation of leukocytes from submicroliters of whole blood was developed. The microcavity array can separate leukocytes from whole blood based on differences in the size and deformability between leukocytes and other blood cells. Leukocytes recovered on aligned microcavities were continuously processed for image-based immunophenotypic analysis. Our device successfully recovered over 90% of leukocytes in 1 µL of whole blood without pretreatment such as density gradient centrifugation or erythrocyte lysis. In addition, the proposed system successfully performed absolute enumeration of human CD4(+) and CD8(+) leukocytes from 1 µL of whole blood, and the obtained data showed good correlation with conventional flow cytometric analysis. Our microfluidic device has great potential as a tool for a point-of-care leukocyte analysis system.


Mechanisms of inactivation of hypothalamic regulatory hormones.
The mechanisms of enzymic inactivation of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone and somatostatin, the three fully-characterized hypothalamic regulatory hormones, and the possible physiological significance of the peptidases in neuroendocrine control has been reviewed. Application of the criteria of enzyme location (at the sites of biosynthesis, release, action, elimination and excretion), appropriate biochemical characteristics of the enzymes and changes in enzyme activity in physiological circumstances all suggest that the peptidases can contribute to the mechanisms controlling the hypothalamic hormones' release and actions. Besides their physiological function, the enzymes may also be directly involved in certain pathological conditions. There is evidence to indicate that the enzymes degrading the regulatory hormones may participate in the process of hormone activation as well as inactivation. A continuing investigation of the peptidases may lead to a better understanding of the established endocrine and other putative functions of these hypothalamic polypeptide hormones.


Regional distribution of kassinin-like immunoreactivity in rat central and peripheral tissues and the effect of capsaicin.
The regional distribution of kassinin-like immunoreactivity in rat central and peripheral tissues was investigated by radioimmunoassay and found to resemble closely that of substance P-like immunoreactivity. Neonatal capsaicin treatment caused a similar decrease to both kassinin-like and substance P-like immunoreactivity in primary sensory areas. These results suggest that more than one member of the tachykinin family of neuropeptides exist within the same neuron.


Distribution of GABA, glycine, and glutamate in neurons of the medulla oblongata and their projections to the midbrain tectum in plethodontid salamanders.
In the medulla oblongata of plethodontid salamanders, GABA-, glycine-, and glutamate-like immunoreactivity (ir) of neurons was studied. Combined tracing and immunohistochemical experiments were performed to analyze the transmitter content of medullary nuclei with reciprocal connections with the tectum mesencephali. The distribution of transmitters differed significantly between rostral and caudal medulla; dual or triple localization of transmitters was present in somata throughout the rostrocaudal extent of the medulla. Regarding the rostral medulla, the largest number of GABA- and gly-ir neurons was found in the medial zone. Neurons of the nucleus reticularis medius (NRM) retrogradely labeled by tracer application into the tectum revealed predominantly gly-ir, often colocalized with glu-ir. The NRM appears to be homologous to the mammalian gigantocellular reticular nucleus, and its glycinergic projection is most likely part of a negative feedback loop between medulla and tectum. Neurons of the dorsal and vestibular nucleus projecting to the tectum were glu-ir and often revealed additional GABA- and/or gly-ir in the vestibular nucleus. Regarding the caudal medulla, the highest density of GABA- and gly-ir cells was found in the lateral zone. Differences in the neurochemistry of the rostral versus caudal medulla appear to result from the transmitter content of projection nuclei in the rostral medulla and support the idea that the rostral medulla is involved in tecto-reticular interaction. Our results likewise underline the role of the NRM in visual object selection and orientation as suggested by behavioral studies and recordings from tectal neurons.


Electrostatic interaction of internal Mg2+ with membrane PIP2 Seen with KCNQ K+ channels.
Activity of KCNQ (Kv7) channels requires binding of phosphatidylinositol 4,5-bisphosphate (PIP(2)) from the plasma membrane. We give evidence that Mg(2+) and polyamines weaken the KCNQ channel-phospholipid interaction. Lowering internal Mg(2+) augmented inward and outward KCNQ currents symmetrically, and raising Mg(2+) reduced currents symmetrically. Polyvalent organic cations added to the pipette solution had similar effects. Their potency sequence followed the number of positive charges: putrescine (+2) < spermidine (+3) < spermine (+4) < neomycin (+6) < polylysine (>>+6). The inhibitory effects of Mg(2+) were reversible with sequential whole-cell patching. Internal tetraethylammonium ion (TEA) gave classical voltage-dependent block of the pore with changes of the time course of K(+) currents. The effect of polyvalent cations was simpler, symmetric, and without changes of current time course. Overexpression of phosphatidylinositol 4-phosphate 5-kinase Igamma to accelerate synthesis of PIP(2) attenuated the sensitivity to polyvalent cations. We suggest that Mg(2+) and other polycations reduce the currents by electrostatic binding to the negative charges of PIP(2), competitively reducing the amount of free PIP(2) available for interaction with channels. The dose-response curves could be modeled by a competition model that reduces the pool of free PIP(2). This mechanism is likely to modulate many other PIP(2)-dependent ion channels and cellular processes.


IL-17 Expression by macrophages is associated with proliferative inflammatory atrophy lesions in prostate cancer patients.
Intraprostatic leukocyte function may vary depending on local inflammatory or malignant cell microenvironment. Interleukin (IL)-17 producing cells play key roles in chronic inflammation and autoimmunity. Little is known about the relevance of IL-17 producing cells at sites of prostate tissue inflammation and/or prostate adenocarcinoma. In this study, we analyzed thirty formalin-fixed paraffin-embedded whole-mount radical prostatectomy specimens of prostate cancer patients. Immunohistochemistry was employed to identify IL-17 producing cells in all sites of mononuclear cell accumulation, noting their relationships to areas of prostate cancer, proliferative inflammatory atrophy (PIA), or hyperplastic benign tissue. Levels of IL-17 producing cells were similar in zones of benign prostate tissue and areas of prostate cancer. Pronounced intraluminal and peri-glandular IL-17 producing cell accumulations were identified in the mononuclear cell infiltrates associated with PIA lesions. Glandular and peri-glandular CD68+ macrophages and neutrophils were the predominant IL-17 producing cells in PIA lesions. The accumulation of IL-17 expressing cells in PIA lesions presents direct evidence of an inflammatory microenvironment that may support the development of prostate cancer.


Serial and single-victim rapists: differences in crime-scene violence, interpersonal involvement, and criminal sophistication.
Three categories of crime-scene behaviors (violence, interpersonal involvement, and criminal sophistication) among a group of 22 serial and 22 single-victim rapists were studied. Findings indicate that serial rapists were more likely to display a higher level of criminally sophisticated behaviors to avoid detection, whereas single-victim rapists were more likely to behave violently and engage in some form of interpersonal involvement with their victims. Implications of these findings for investigation and for understanding offenders' behavior are discussed.


Management of ischemic tissues and skin flaps in Re-Operative and complex hypospadias repair using vasodilators and hyperbaric oxygen.
Repeated and multiple surgeries for hypospadias result in varying degrees of scarring and hypovascularity of penile tissues which may result in poor healing and increasing complication rates with each additional repair. Vasodilator agents such as Nitroglycerine (NTG) can be helpful in the immediate postoperative period to improve flap viability. Hyperbaric oxygen therapy (HBOT) has well-established benefits to promote angiogenesis and wound healing. We hypothesized that NTG and HBOT, methods to promote blood flow and wound healing, would provide better outcomes in redo hypospadias surgeries and reduce complication rates; and, that HBOT and NTG would provide better outcomes compared to NTG alone. Herein, the authors review the results of their strategy of the past 5.5 years in managing these compromised hypovascular tissues using 2% NTG and HBOT for redo surgery of hypospadias. Between 2014 and 2019, 82 patients (2-24 years old) exhibiting varying degrees of scarring of skin and subcutaneous tissues underwent re-operative repair of hypospadias complications following failed surgeries (3-9 operations, average 5.5 failed previous repairs). There were two groups of patients: Group I (49 patients) received trimodal therapy consisting of NTG, HBOT, and local steroids. The patients were examined every 3 weeks and every 3 months thereafter. The postoperative site was photographed by the parents or by the older patient prior to each visit. Group II (33 patients) received NTG and local steroids, but not HBOT for various reasons. In Group I: 44/49 (88.8%) of the repairs were successful. The complications in this group included a distal repair breakdown (n = 2) and urethral fistula (n = 3). In Group II, a successful outcome was noted in 23/33 (69.6%). The follow up of the 78 patients who completed their repairs varied between 5 months and 4 years. Results are highlighted in the table. In accordance to previously published data, the study results further support promising outcomes of application of NTG and HBOT to improve flap viability. Limitations include non-randomization of our treatment groups resulting in a retrospective evaluation of our protocol; and, the intrinsic heterogeneity of our patient population, previous surgical repairs, and scar tissues. The proposed treatment of combining NTG and HBOT appears to result in reversal of tissue hypoxia and improved wound healing. This preliminary report shows improved outcomes with less morbidity in a group of patients with multiple hypospadias surgical failures and it warrants further application in a larger number of patients.


Quality of the handover of patient care: a comparison of pre-Hospital and Emergency Department notes.
The aim of this audit was to evaluate the accuracy of patient information transfer from pre-hospital reports to Emergency Department (ED) documentation. The records of 100 patients seen in the ED resuscitation room of a UK hospital were compared using a pro-forma designed by the research team. Sections of the ambulance service patient report form and the ED documentation were compared for differences. The history of the event leading to the 999 call, the patient's previous medical history, prescribed medications, allergies and any treatment carried out by the ambulance crew were analysed. Of the 100 records, 26 had at least one instance where information recorded by the ambulance crew was either omitted or altered during transfer. These fell into various categories including the previous medical history of the patient, the timings of the event bringing them to hospital, frequency of the event occurring, allergies and medications. This audit quantifies the number of patient encounters where written information changes or is lost when care is passed from pre-hospital to hospital staff in the resuscitation room. We have not investigated other parts of the ED or the verbal transfer of information. Further work investigating the causes of these changes in information, any impact on patient care and whether this occurs in other parts of an ED is suggested.


Discovery of Sound in the Sea: Resources for Educators, Students, the Public, and Policymakers.
There is increasing concern about the effects of underwater sound on marine life. However, the science of sound is challenging. The Discovery of Sound in the Sea (DOSITS) Web site ( http://www.dosits.org ) was designed to provide comprehensive scientific information on underwater sound for the public and educational and media professionals. It covers the physical science of underwater sound and its use by people and marine animals for a range of tasks. Celebrating 10 years of online resources, DOSITS continues to develop new material and improvements, providing the best resource for the most up-to-date information on underwater sound and its potential effects.


Evaluation of color Doppler ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of breast cancer.
To evaluate the clinical value of color Doppler ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of breast cancer (BC). 129 patients with BC and 50 patients with benign breast lesions were selected. They were scanned by color Doppler ultrasound on the breast. The relative expression of miR-21 and miR-27a in plasma was detected by real-time fluorescence quantitative PCR. The clinical value of color Doppler ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of BC was analyzed retrospectively. Two-dimensional ultrasound images of BC showed irregular shape, unclear boundary, burr-like edge, uneven internal echo, weakened rear echo, microcalcification, aspect ratio > 1 and axillary lymph node metastasis. The grade of blood flow signal was improved, mainly in grade II and above, which was statistically different from that of benign control group (P < 0.001). The relative expression of plasma miR-21 and miR-27a in breast cancer group was significantly higher than that in benign control group (P < 0.001). The relative expressions of plasma miR-21 and miR-27a in breast cancer group were significantly correlated with histological grade, clinical stage, lymph node metastasis and postoperation. The relative expression levels of miR-21 and miR-27a in plasma of patients with low histological grade (grade III), high clinical stage (stage III, IV) and lymph node metastasis before operation were significantly higher than those in patients with high histological grade (grade I, II), low clinical stage (stage I, II) and no lymph node metastasis after operation (P < 0.01). The sensitivity, accuracy and negative predictive value of ultrasound combined with plasma miR-21 and miR-27a in the diagnosis of BC were significantly higher than those of each single examination. Color Doppler ultrasound combined with plasma miR-21 and miR-27a can significantly improve the diagnostic efficiency of BC, which is beneficial to early diagnosis and early clinical intervention.


Cardiac arrhythmic response evoked by stimulation of fastigial nuclei in the anesthetized cat.
Using the Horsley-Clarke sterotaxic technique for positioning electrodes in the cerebellum of the cat, the present study has shown that electrical stimulation of the nucleus fastigius produces cardiac arrhythmia in addition to the already known pressor response. These arrhythmias ranged from sinus tachycardia to various kinds of ectopic beats, and the effects of the arrhythmias on cardiovascular haemodynamics are discussed. Administration of the beta-adrenergic-blocking drug (propranolol) and the adrenergic neuron-blocking drug (bretylium tosylate) showed that the cardiac arrhythmic responses were predominantly due to sympathetic activation. Bilateral cervical vagotomy facilitated the production of ectopic beats during fastigial stimulation, but either abolished those ectopic beats previously arising in the post-stimulation period or modified them to the extent that they characteristically became beats with short P-R intervals and wide QRS complexes. This evidence indicates a cerebellar control of autonomic system functions.


Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation.
Establishment of oligodendrocyte identity is crucial for subsequent events of myelination in the CNS. Here, we demonstrate that activation of ATP-dependent SWI/SNF chromatin-remodeling enzyme Smarca4/Brg1 at the differentiation onset is necessary and sufficient to initiate and promote oligodendrocyte lineage progression and maturation. Genome-wide multistage studies by ChIP-seq reveal that oligodendrocyte-lineage determination factor Olig2 functions as a prepatterning factor to direct Smarca4/Brg1 to oligodendrocyte-specific enhancers. Recruitment of Smarca4/Brg1 to distinct subsets of myelination regulatory genes is developmentally regulated. Functional analyses of Smarca4/Brg1 and Olig2 co-occupancy relative to chromatin epigenetic marking uncover stage-specific cis-regulatory elements that predict sets of transcriptional regulators controlling oligodendrocyte differentiation. Together, our results demonstrate that regulation of the functional specificity and activity of a Smarca4/Brg1-dependent chromatin-remodeling complex by Olig2, coupled with transcriptionally linked chromatin modifications, is critical to precisely initiate and establish the transcriptional program that promotes oligodendrocyte differentiation and subsequent myelination of the CNS.


Ultrasonography of anterosuperior calcaneal process fracture: report of 2 cases.
The purpose of this series is to describe the ultrasonographic findings of anterosuperior calcaneal process (ASCP) fracture. Two patients with ASCP fractures were examined with ultrasonography. Both of them had pain over the lateral aspect of the ankle 10 to 13 months after an injury. Initial radiographs had shown no evidence of bone fracture or bone avulsion. In both cases, ultrasonography revealed the presence of a bone fragment adjacent to the ASCP suggestive of a misdiagnosed fracture. The latter was confirmed by radiographs. In 1 case, a hypoechoic thickening of the calcaneocuboid component of the bifurcate ligament was also identified on ultrasonographic scans. Ultrasonography is potentially valuable in detecting clinically or radiographically occult ASCP fractures.