Staff perceptions of barriers to physical restraint-reduction in long-term care: a meta-synthesis.
To critically review the existing qualitative studies to identify, from the perspective of staff, the barriers to physical restraint reduction in long-term geriatric care facilities. Despite the adverse physical and psychosocial effects, physical restraints are still used frequently in many geriatric long-term care facilities around the world. There is, however, no study that synthesises the existing qualitative literature regarding the barriers to the restraint reduction from the perspective of facility staff. The metastudy research process guided this qualitative synthesis. Five electronic databases were searched, and ten studies were included in this metastudy. Five themes were identified through metasynthesis of the findings: concern about and responsibility for safety, unclear and inconsistent definitions of restraint and restraint-free care, difficulties in the transition from acceptance to removal, noninvolvement in decision-making to remove restraint and insufficient resources and education. A concept analysis of physical restraint is sorely needed, and future studies should explore the prevalence of restraint, the effects of education for staff and family on restraint reduction, and success stories related to restraint-free care. More research is needed regarding the restraint reduction effectiveness and cost issues. Physical restraints, commonly used in many geriatric long-term care facilities, result in many negative effects and ethical issues. To achieve success in reducing physical restraint use, governmental policies and long-term care institutions should underpin staff efforts with legal, educational and practical support.


Ultrastructure of the rete testis in the cat (Felis domestica, L.).
The rete testis (RT) in the cat comprises three distinct and sequential parts: septal or adlobular; mediastinal and tunical parts. This last part is followed by the small extratesticular rete testis. The whole of the RT tubules and/or channels is lined by single low columnar and/or cuboidal epithelium with ultrastructural peculiarities of secretory and absorptive functions. The Golgi apparatus polarity (cis-trans surfaces), its relation with the long profiles of the ER, mainly with the rough ER, and presence of apical uncoated electrodense granules are suggestive of active release of macromolecules, probably glycoproteins. The absorptive function is proposed through the observation of a conspicuous microvacuolar-vesicular apical complex in epithelial cells. Moreover spermatozoa phagocytosis is also noticed, mainly in the septal part of the RT.


A multi-center analysis evaluating factors associated with spinal cord stimulation outcome in chronic pain patients.
In addition to its conventional use as a treatment for refractory neuropathic extremity pain, spinal cord stimulation (SCS) has recently emerged as a possible treatment for visceral and arthritic pain. But concurrent with the expansion of possible conditions amenable to SCS, other studies have questioned the long-term efficacy of SCS for traditional indications. These disparate findings argue strongly for the refinement of selection criteria. The purpose of this study is to identify correlates of outcome for SCS. Data were retrospectively collected on 244 patients who underwent a SCS trial at two academic medical centers. Success was predefined as ≥50% pain relief sustained for ≥6 months. Variables analyzed for their association with outcome included demographics, location of pain, diagnosis, presence of coexisting diseases, pain descriptors, opioid and adjuvant medication use, duration and pain relief during trial, and complications. The presence of allodynia and/or hyperalgesia correlated with both a positive SCS trial (P = 0.01) and long-term implantation outcome (P = 0.05). History of substance abuse was associated with a negative permanent SCS outcome (P = 0.05) but bore no relationship to trial results. The variable most strongly associated with an SCS outcome was experiencing <50% pain relief during the trial, which strongly presaged a negative result (P < 0.001). Although weak associations with outcome were noted for several clinical variables, none was strongly associated with trial and permanent implantation results. The strongest predictor of a negative SCS outcome was obtaining <50% pain relief during the trial period.


Determining the arsenic, cadmium, lead, copper and chromium contents by atomic absorption spectrometry in Pangasius fillets from Vietnam.
Pangasius is a fish produced on a large scale in Vietnam and exported to many countries. Since river contamination from human activities can affect the safety of this food, fish consumption can cause exposure to potentially toxic elements for humans. The aim of this study, therefore, was to assess arsenic, cadmium, lead, copper and chromium contents by atomic absorption spectrometry in Pangasius fillet produced in the provinces of Dong Thap and Can Tho (Vietnam) and exported to Brazil. The limits of detection were: arsenic 0.5443 µg kg(-1) , cadmium 0.0040 mg kg(-1) , chromium 0.0004 mg kg(-1) , copper 0.0037 mg kg(-1) and lead 0.0284 mg kg(-1) . Analysis of 20 samples showed results below the limit of detection for arsenic, chromium and lead, while copper average concentration was 0.0234 mg kg(-1) . Cadmium average concentration was 0.0547 mg kg(-1) , with no significant difference between the two regions studied. The samples of Pangasius had no detectable concentrations of arsenic, chromium, copper and lead, and do not represent a hazard to public health. However, cadmium analysis revealed non-compliant samples, demonstrating the importance of monitoring the quality of imported Pangasius fish. © 2015 Society of Chemical Industry.


Restoring p53 tumor suppressor activity as an anticancer therapeutic strategy.
Loss of p53 tumor suppressor function is a key event in the genesis of most human tumors. This observation has prompted efforts to restore p53 activity as an anticancer therapeutic approach. Recent developments that have extended our understanding of how p53 activity is regulated and how mutations disrupt that regulation have provided the insight needed to develop therapeutic strategies that take advantage of this knowledge. In this article, we review the strategies for restoring p53 function and some of the new compounds that show promise as antitumor agents in preclinical models.


Prehypertension and risk for all-cause and cardiovascular mortality by diabetes status: results from the national health and nutrition examination surveys.
It is unclear whether prehypertension alone or combined with diabetes associate with a higher risk for cardiovascular or all-cause mortality. The purpose of this study was to explore the relationship between prehypertension and all-cause and cardiovascular mortality stratified by diabetes status. All participants aged ≥18 years were enrolled from the 1999-2014 National Health and Nutrition Examination Surveys (NHANES). Prehypertension was defined as systolic/diastolic blood pressure (BP): 120-139/80-89 mmHg. The status of cardiovascular and all-cause mortality of participants were followed up through 31 December 2015. We performed Cox proportional hazards models and Kaplan-Meier survival curves to evaluate the relationships as mentioned above. In general, we enrolled 26,070 participants while 15,295 (58.67%) of them did not have diabetes nor prehypertension, 8,870 (34.02%) had prehypertension alone, 835 (3.20%) had diabetes alone, and 1,070 (4.11%) had both diabetes and prehypertension. Compared with participants without diabetes nor prehypertension, the multivariable adjusted hazard ratios and 95% confidence interval (CI) for all-cause mortality among participants with prehypertension alone, diabetes alone, and both diabetes and prehypertension were 1.08 (95% CI: 0.95, 1.23), 1.26 (0.98, 1.62), and 1.67 (1.38, 2.03) (P for trend <0.001), for cardiovascular mortality, the corresponding hazard ratios and 95% CI were 1.40 (95% CI: 0.92, 2.14), 2.21 (1.12, 4.38), and 2.87 (1.65, 4.99) (P for trend <0.001) respectively. Our findings suggested that prehypertension associated with an increased risk for cardiovascular and all-cause mortality when compared with diabetes, but not for prehypertension alone. Early screening and intervention for BP among diabetic patients may be beneficial.


Hemopoietins: roles in inflammation, allergy and neoplasia.
Cytokines link keratinocytes with lymphocytes and the specialized phagocytic and granulocytic cells of the hemopoietic system and are critical elements in the response of the skin to invasion or injury. The cytokine network is complex and includes potential autoregulatory circuits. A better understanding of these networks and of the function and structure of cytokines may lead to a more rational approach to the design of drugs and to new treatments.


Label propagation defines signaling networks associated with recurrently mutated cancer genes.
Human tumors have distinct profiles of genomic alterations, and each of these alterations has the potential to cause unique changes to cellular homeostasis. Detailed analyses of these changes could reveal downstream effects of genomic alterations, contributing to our understanding of their roles in tumor development and progression. Across a range of tumor types, including bladder, lung, and endometrial carcinoma, we determined genes that are frequently altered in The Cancer Genome Atlas patient populations, then examined the effects of these alterations on signaling and regulatory pathways. To achieve this, we used a label propagation-based methodology to generate networks from gene expression signatures associated with defined mutations. Individual networks offered a large-scale view of signaling changes represented by gene signatures, which in turn reflected the scope of molecular events that are perturbed in the presence of a given genomic alteration. Comparing different networks to one another revealed common biological pathways impacted by distinct genomic alterations, highlighting the concept that tumors can dysregulate key pathways through multiple, seemingly unrelated mechanisms. Finally, altered genes inducing common changes to the signaling network were used to search for genomic markers of drug response, connecting shared perturbations to differential drug sensitivity.


The sigma(E) and the Cpx signal transduction systems control the synthesis of periplasmic protein-folding enzymes in Escherichia coli.
In Escherichia coli, the heat shock-inducible sigma-factor sigma(E) and the Cpx two-component signal transduction system are both attuned to extracytoplasmic stimuli. For example, sigma(E) activity rises in response to the overproduction of various outer-membrane proteins. Similarly, the activity of the Cpx signal transduction pathway, which consists of an inner-membrane sensor (CpxA) and a cognate response regulator (CpxR), is stimulated by overproduction of the outer-membrane lipoprotein, NlpE. In response to these extracytoplasmic stimuli, sigma(E) and CpxA/CpxR stimulate the transcription of degP, which encodes a periplasmic protease. This suggests that CpxA/CpxR and sigma(E) both mediate protein turnover within the bacterial envelope. Here, we show that CpxA/CpxR and sigma(E) also control the synthesis of periplasmic enzymes that can facilitate protein-folding reactions. Specifically, sigma(E) controls transcription of fkpA, which specifies a periplasmic peptidyl-prolyl cis/trans isomerase. Similarly, the Cpx system controls transcription of the dsbA locus, which encodes a periplasmic enzyme required for efficient disulfide bond formation in several extracytoplasmic proteins. Taken together, these results indicate that sigma(E) and CpxA/CpxR are involved in regulating both protein-turnover and protein-folding activities within the bacterial envelope.


[Umbilical hernia in children].
Umbilical hernia is a common condition in the pediatric population. EMBRYOLOGY: Umbilical hernia is a consequence of incomplete closure or weakness at the umbilical ring, where protrusion of intraabdominal contents may occur. Fascia posterior to the canal is thinner, creating an area of weakness. Congenital or direct hernia occurs in this area, while herniation in the umbilical canal leads to indirect or acquired hernia. The incidence of umbilical hernia is 1.9% to 18.5% in white population. The great majority of pediatric umbilical hernias are asymptomatic. Incarceration and strangulation are uncommon. Rupture of umbilical hernia with resultant evisceration is extremely rare. Umbilical hernia may also be the source of intermittent umbilical or abdominal pain. Treatment options for umbilical hernias range from simple observation to surgical repair. The great majority close spontaneously and observation with periodic follow-up is appropriate in most cases. There are no available data to suggest that strapping improves or accelerates closure. Operation would be recommended for defects greater than 1 cm, by the age 3 to 4. Persistence or enlargement of fascial defect during the period of observation are reasons to consider repair, whatever the age. Complications of operative repair of umbilical hernias include those related to anesthesia and local wound infections. Umbilical hernia is a common condition among infants and children. In the great majority of cases, the natural history is one of eventual closure without treatment. If spontaneous closure does not occur until the age of 3-4 years, operative correction is recommended.


English historical demography and the nuptiality conundrum: new perspectives.
"In the last decade, nuptiality has been placed at the centre of the English demographic regime in the long eighteenth-century. Proto-industrial areas in particular are increasingly seen to have experienced substantial decline in the female age at first marriage during this period, helping to fuel substantial population growth. This article uses family reconstitution and other data to question the uniformity of this experience and to suggest new avenues of interpretation rather than simply observation. For Calverley in West Yorkshire, England, female marriage ages remained stable throughout the proto-industrialisation process. More significantly, the distribution of marriage ages around the mean was much narrower than similar measures elsewhere. The article suggests that kinship, a deep sentimental and practical attachment to land, and an early retirement system lay behind this experience."


Exogenous H2S protects H9c2 cardiac cells against high glucose-induced injury and inflammation by inhibiting the activation of the NF-κB and IL-1β pathways.
Hyperglycemia has been reported to activate the nuclear factor-κB (NF-κB) pathway. We have previously demonstrated that exogenous hydrogen sulfide (H2S) protects cardiomyocytes against high glucose (HG)-induced injury by inhibiting the activity of p38 mitogen-activated protein kinase (MAPK), which can activate the NF-κB pathway and induce interleukin (IL)-1β production. In the present study, we aimed to investigate the hypothesis that exogenous H2S protects cardiomyocytes against HG-induced injury and inflammation through the inhibition of the NF-κB/IL-1β pathway. H9c2 cardiac cells were treated with 35 mM glucose (HG) for 24 h to establish a model of HG-induced damage. Our results demonstrated that treatment of the cells with 400 µM sodium hydrogen sulfide (NaHS, a donor of H2S) or 100 µM pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB) for 30 min prior to exposure to HG markedly attenuated the HG-induced increase in the expression levels of the phosphorylated (p)-NF-κB p65 subunit. Notably, pre-treatment of the H9c2 cardiac cells with NaHS or PDTC significantly suppressed the HG-induced injury, including cytotoxicity, apoptosis, oxidative stress and mitochondrial insults, as evidenced by an increase in cell viability, as well as a decrease in the number of apoptotic cells, the expression of cleaved caspase-3, the generation of reactive oxygen species (ROS) and the dissipation of mitochondrial membrane potential (MMP). In addition, pre-treatment of the cells with NaHS or PDTC ameliorated the HG-induced inflammatory response, leading to a decrease in the levels of IL-1β, IL-6 and tumor necrosis factor-α (TNF-α). Importantly, co-treatment of the H9c2 cells with 20 ng/ml IL-1 receptor antagonist (IL-1Ra) and HG markedly reduced the HG-induced increase in p-NF-κB p65 expression, cytotoxicity, the number of apoptotic cells, as well as the production of TNF-α. In conclusion, the present study presents novel mechanistic evidence that exogenous H2S protects H9c2 cardiac cells against HG-induced inflammation and injury, including cytotoxicity, apoptosis, overproduction of ROS and the dissipation of MMP, by inhibiting the NF-κB/IL-1β pathway. We also provide new data indicating that the positive interaction between the NF-κB pathway and IL-1β is critical in HG-induced injury and inflammation in H9c2 cardiac cells.


Head-Eye Coordination Increases with Age and Varies across Countries.
Head movements in older people may contribute to their dizziness and equilibrium problems. Head gain is the ratio of head movement to total movement (head + eye) when executing a saccade to an eccentric target. Two studies have investigated the relationship between head gain and age but have provided conflicting results. We report head gain data collected from research laboratories and optician stores. Our sample sizes are much larger (n = 657 for laboratory, n = 64,458 for optician stores), permitting more detailed analyses. The head-eye coefficient, expressed as 100 times the square root of head gain, was bimodal with one mode of primarily eye movers and one mode of eye-and-head movers. Head-eye coefficient increased with age and was invariant with eye correction and gender. We also found an effect of nation that seemed associated with gross domestic product or by latitude (in the northern hemisphere) and log population density. Assuming that head movements and visual distortions contribute to dizziness and equilibrium problems, our study suggests that customizing eyewear based on age and country may help in reducing the prevalence of problems associated with head and/or eye movements.


Spillover of Medicaid Expansion to Prescribing of Opioid Use Disorder Medications in Medicare Part D.
The authors examined whether there were positive spillovers in opioid use disorder medication prescribing to Medicare Part D beneficiaries in Medicaid expansion states. Although prior studies have shown several positive benefits of Medicaid expansion for Americans with opioid use disorder, research has not examined potential spillovers to Medicare beneficiaries who have been hit hard by the opioid crisis. Prescribing data were taken from the Medicare Part D Prescription Public Use File (2010-2017). A difference-in-differences linear regression framework was used to identify spillovers in prescribing of buprenorphine and injectable naltrexone to Medicare Part D beneficiaries in Medicaid expansion states. Three sets of dependent variables measured medication prescribing at the county-year level (N=24,850). All models included county and year fixed effects, with standard errors clustered at the state level to address within-state serial correlation. Medicaid expansion was associated with an increase in the probability of a county having an injectable naltrexone provider (p<0.01). After expansion, the number of buprenorphine providers in expansion states increased by 5.6% (p<0.05), and the number of injectable naltrexone providers increased by 3.3% (p<0.01), relative to nonexpansion states. Expansion was associated with a 23.1% (p<0.01) increase in the number of daily doses of injectable naltrexone, relative to nonexpansion states. Medicaid expansion states may be better equipped to address the opioid crisis because of direct benefits to Medicaid beneficiaries and availability of opioid use disorder medications for Medicare Part D beneficiaries. However, additional efforts are likely needed to close the opioid use disorder treatment gap for Medicare beneficiaries.


[HPLC study of the pharmacokinetics of mezlocillin administered by 30-minute infusion and comparison with the direct intravenous route].
Mezlocillin pharmacokinetics were investigated in eighteen patients from a surgical service after a 30 minutes infusion with the purpose, on one hand, to compare this way of administration with a bolus intravenous infusion, and on the other hand to confirm or invalidate capacity-limited dose-dependent pharmacokinetics. Dosages were 2 g (n = 8) and 5 g (n = 10). Mezlocillin levels were measured by high performance liquid chromatography. Calculated data obtained with the 30 minutes infusion are different from those resulting from a bolus infusion. Peak levels, alpha and beta are lower ; T 1/2 beta, areas under the curve, and distribution volumes are higher. Most of the calculated data were not in agreement with a capacity-limited kinetic at the two studied dosages. The two regression-lines (2 g and 5 g) of mezlocillin body clearance versus creatinine clearance superimpose exactly. The 30 minutes infusion, and important hemodynamic variations between our 18 patients may partly explain the differences between our data and those published in the literature.


Esophageal involvement in Wegener's granulomatosis.
Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis, renal disease, and upper and lower respiratory tract disease. Although most organ systems can be involved, gastrointestinal (GI) manifestations are notably uncommon. We describe a patient with WG whose presentation was unique for the prominence of odynophagia. Esophagoscopy revealed erosive esophagitis, which on biopsy was shown to be due to direct involvement by the underlying vasculitis. This is first antermortem documentation of esophageal disease secondary to WG. The GI manifestations of WG are reviewed.


Movement Demands and Running Intensities of Semi-Professional Rugby League Players during A 9's Tournament: A Case Study.
The objective of the study was to describe the movement demands and running intensities of semi-professional rugby league players during a rugby league 9's (RL9's) tournament. Six semi-professional rugby league players competed in a RL9's tournament over a two-day period comprising of six games. Movement demands and running intensities were recorded using Global Positioning System (GPS) devices providing data on distance and speeds. Data is presented as mean (95% Confidence Intervals) with changes (≥ 75%) likely to exceed the smallest worthwhile change (0.2) considered practically important. Outside backs performed significantly (p < 0.05) more relative VHSR (3.9 m [3.5-4.3] vs 2.4 m [2.1-2.8]) absolute (97.7 m [81.3-114.1] vs 22.6m [15.8-29.3]) and relative (5.0 m·min-1 [4.2-5.9] vs 1.2 m·min-1 [0.8-1.6]) sprint distance than the forwards. Outside backs also performed significantly (p < 0.05) more absolute (97.7 m [81.3-114.1] vs 43.9 m [27.2-60.7]) and relative (5.0 m·min-1 [4.2-5.9] vs 2.3 m·min-1 [1.4-3.2]) sprint distance than the adjustables. Moderate (0.6 - 1.2) to very large (> 2.0) decreases in performance variables were observed over the two days. The biggest magnitude of change over the two days was seen with very large decreases in relative HSR (- 2.10) and sprint (- 2.14) distance. Between playing groups, the outside backs had the biggest decrease in running intensity with a very large (- 2.32) significant (p < 0.05) decrease in VHSR on day 2 (3.3 m·min-1 [2.5 - 4.1]) compared to day 1 (4.9 m·min-1 [4.4 - 5.4]). Running intensities are decreased during an intensified RL9's tournament in semi-professional rugby league players. The observed decreases in running performances between playing groups are in agreement with previous research and may support the use of individualized player monitoring and recovery management during a RL9's tournament-style competition.


Development of the platysma muscle and the superficial musculoaponeurotic system (human specimens at 8-17 weeks of development).
There is controversy regarding the description of the different regions of the face of the superficial musculoaponeurotic system (SMAS) and its relationship with the superficial mimetic muscles. The purpose of this study is to analyze the development of the platysma muscle and the SMAS in human specimens at 8-17 weeks of development using an optical microscope. Furthermore, we propose to study the relationship of the anlage of the SMAS and the neighbouring superficial mimetic muscles. The facial musculature derives from the mesenchyme of the second arch and migrates towards the different regions of the face while forming premuscular laminae. During the 8th week of development, the cervical, infraorbital, mandibular, and temporal laminae are observed to be on the same plane. The platysma muscle derives from the cervical lamina and its mandibular extension enclosing the lower part of the parotid region and the cheek, while the SMAS derives from the upper region. During the period of development analyzed in this study, we have observed no continuity between the anlage of the SMAS and that of the superficial layer of the temporal fascia and the zygomaticus major muscle. Nor have we observed any structure similar to the SMAS in the labial region.


A novel VWF variant associated with type 2 von Willebrand disease in German Wirehaired Pointers and German Shorthaired Pointers.
Von Willebrand disease (VWD), caused by deficiency of the von Willebrand factor (VWF), is the most common bleeding disorder in humans and dogs. The complete cDNA encoding VWF of a German Wirehaired Pointer with type 2 VWD was sequenced, and we found four variants that alter the amino acid sequence. These variants were: c.1657T>G corresponding to p.Trp553Gly; c.1777G>A (p.Glu593Lys); c.4937A>G (p.Asn1646Ser) and c.5544G>A (p.Met1848Ile). A haplotype of the c.1657G, c.1777A and c.4937G alleles co-segregated with the VWF antigen level in a four-generation pedigree with the disease. Healthy dogs of the breed were found that were homozygous for the c.1777A or the c.5544A allele, indicating that these variants do not cause VWD. Dogs that were homozygous for the c.4937G allele and had no signs of a bleeding disorder were observed in the Chinese Crested dog breed. Thus, only the c.1657G variant was found in the homozygous state exclusively in VWD affecteds, and this variant is the strongest candidate to be the cause of VWD type 2 in the German Wirehaired Pointer breed. A screen of German Shorthaired Pointers indicated that the variant also segregates with VWD in this breed.


Temperate forest methane sink diminished by tree emissions.
Global budgets ascribe 4-10% of atmospheric methane (CH4 ) sinks to upland soils and have assumed until recently that soils are the sole surface for CH4 exchange in upland forests. Here we report that CH4 is emitted from the stems of dominant tree species in a temperate upland forest, measured using both the traditional static-chamber method and a new high-frequency, automated system. Tree emissions averaged across 68 observations on 17 trees from May to September were 1.59 ± 0.88 μmol CH4 m-2 stem h-1 (mean ± 95% confidence interval), while soils adjacent to the trees consumed atmospheric CH4 at a rate of -4.52 ± 0.64 μmol CH4 m-2 soil h-1 (P < 0.0001). High-frequency measurements revealed diurnal patterns in the rate of tree-stem CH4 emissions. A simple scaling exercise suggested that tree emissions offset 1-6% of the growing season soil CH4 sink and may have briefly changed the forest to a net CH4 source.


Experiences with allopurinal in canine endotoxin shock.
Allopurinol, a xanthine-oxidase inhibitor and potential cell-stabilizing compound, was studied as a possible therapeutic agent in canine endotoxin shock. Circulatory collapse was produced in anesthetized mongrel dogs by IV administration of an LD75 dose of endotoxin. Treatment, with dextran alone, or with dextran and an IV bolus of allopurinol, was initiated 15 minutes after the onset of shock. The administration of 25, 50, or 100 mg/kg of IV allopurinol, accompanied by adequate volume replenishment, produced a significant reduction in the total peripheral vascular resistance and significant increases in cardiac output, blood glucose concentration, and arterial lactate concentration. Survival was not enhanced by allopurinol therapy, and allopurinol administration in normal dogs did not affect the vascular tone or the arterial lactic acid concentration. There was a transient hyperglycemic response and a decrease in the cardiac index in normal animals. The infusion of a postassium-insulin solution, in association with 100 mg/kg of allopurinol, did not significantly improve survival. In summary, although a number of potentially beneficial hemodynamic and metabolic effects were observed following allopurinol administration, survival in canine endotoxin shock was not enhanced.


Fat crystals: A tool to inhibit molecular transport in W/O/W double emulsions.
Water-in-oil-in-water (W/O/W) double emulsions are a promising technology for encapsulation applications of water soluble compounds with respect to functional food systems. Yet molecular transport through the oil phase is a well-known problem for liquid oil-based double emulsions. The influence of network crystallization in the oil phase of W/O/W globules was evaluated by NMR and laser light scattering experiments on both a liquid oil-based double emulsion and a solid fat-based double emulsion. Water transport was assessed by low-resolution NMR diffusometry and by an osmotically induced swelling or shrinking experiment, whereas manganese ion permeation was followed by means of T2 -relaxometry. The solid fat-based W/O/W globules contained a crystal network with about 80% solid fat. This W/O/W emulsion showed a reduced molecular water exchange and a slower manganese ion influx in the considered time frame, whereas its globule size remained stable under the applied osmotic gradients. The reduced permeability of the oil phase is assumed to be caused by the increased tortuosity of the diffusive path imposed by the crystal network. This solid network also provided mechanical strength to the W/O/W globules to counteract the applied osmotic forces.


Listening in family psychotherapy.
The author describes with clinical examples why the neglected tool of listening is of vital importance in supervising and practising family psychotherapy. This neglect is highlighted as a possible side effect of focussing exclusively on the use of one way mirrors and video equipment in teaching family psychotherapy.


Serum Trace Elements in Children with End-Stage Renal Disease.
Trace elements, which have a crucial role in metabolism and enzymatic pathways, are not routinely monitored in the blood of pediatric patients with chronic kidney disease. The present study was carried out to determine the serum levels of copper (Cu), zinc (Zn), selenium (Se), and lead (Pb) in children with ESRD who were currently receiving conservative management or were on long-term hemodialysis or continuous ambulatory peritoneal dialysis. This study involved 200 children who met the inclusion criteria. The children were divided into 4 groups: a hemodialysis group, a peritoneal dialysis group, a group of children with ESRD treated with conservative management, and a control group. Serum levels of Zn, Cu, Se, and Pb were evaluated using an atomic absorption spectrophotometer and compared between the groups. There was no significant difference in the serum concentration of Cu among the 4 study groups. There was also no significant difference in the serum concentrations of Zn, Se, and Pb between healthy children and children with CKD treated with conservative management or between the hemodialysis and peritoneal dialysis groups. The levels of Zn and Se were significantly lower in the hemodialysis and peritoneal dialysis groups than in the healthy children or in children with CKD treated with conservative management. The level of Pb in the blood was significantly lower in healthy children and children with CKD treated with conservative management than in the hemodialysis or peritoneal dialysis groups. The levels of trace elements were substantially different between the dialysis groups and healthy children and children with CKD treated with conservative management. These results highlighted the role of osmosis during dialysis, as dialysate impurities can cause a disturbance in the levels of trace elements and the role of the kidney, even with minimum residual function, in the homeostasis of trace elements.


Development of an analytical method for the determination of antidepressants in water samples by capillary electrophoresis with electrospray ionization mass spectrometric detection.
A method for the quantitative determination of major antidepressants in aqueous matrices by CE using ESI-MS is presented. Several aqueous, nonaquoeus, and mixed aqueous/organic solvent BGEs including inorganic and organic acids were investigated with respect to their suitability for the separation of the selected analytes. Finally, due to the necessity to employ MS detection if the developed method should be suitable also for environmental samples, only MS-compatible electrolytes were taken into account. Based on this fact optimum results were obtained with a system consisting of 1.5 M formic acid and 50 mM ammonium formate in ACN/water (85/15). Linear calibration plots could be obtained for all solutes over a concentration range of almost two orders of magnitude, and the LODs achieved were in the range of 3-6 microg/L for trazodone and 39-43 microg/L for sertraline with the TOF instrument and the single quadrupole instrument in the SIM mode, respectively. This fact allowed the assumption that the presented method can be regarded as suitable for the determination of antidepressants even in the trace amounts commonly present in environmental samples. Spiking of river water and sewage plant effluent extracts with the selected solutes showed that no interferences from the matrix usually found in such samples can be expected. Finally the quantitative determination of the seven antidepressants in environmental samples was used to benchmark the performance of CZE coupled to a single quadrupole MS and a TOF-MS.


Successful treatment of refractory pure red cell aplasia associated with lymphoproliferative disorders with the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H).
Acquired pure red cell aplasia (PRCA) is a rare, but significant, complication of lymphoproliferative disorders. It is characterized by anaemia, absence of red cell precursors in the bone marrow and normal granulopoiesis and megakaryopoiesis. We describe two patients with refractory pure red cell aplasia associated with chronic lymphocytic leukaemia (CLL) and a large granular CD8 T-lymphocytic leukaemia (LGL) respectively. Both patients had failed multiple treatment regimens for PRCA and were transfusion dependent. Both patients were subsequently treated with the anti-CD52 humanized monoclonal antibody, alemtuzumab, receiving total doses in excess of 300 mg. Response to treatment, as documented by a rapid increase in the reticulocyte count, occurred as early as the third infusion. At the time of this report, both patients remain in complete remission with normal haemoglobin levels. Alemtuzumab appears to be an effective and well-tolerated therapy for pure red blood cell aplasia associated with lymphoproliferative disorders.


Developing an Intelligent System for Diagnosis of Asthma Based on Artificial Neural Network.
Lack of proper diagnosis and inadequate treatment of asthma, leads to physical and financial complications. This study aimed to use data mining techniques and creating a neural network intelligent system for diagnosis of asthma. The study population is the patients who had visited one of the Lung Clinics in Tehran. Data were analyzed using the SPSS statistical tool and the chi-square Pearson's coefficient was the basis of decision making for data ranking. The considered neural network is trained using back propagation learning technique. According to the analysis performed by means of SPSS to select the top factors, 13 effective factors were selected, in different performances, data was mixed in various forms, so the different modes was made for training the data and testing networks and in all different modes, the network was able to predict correctly 100% of all cases. Using data mining methods before the design structure of system, aimed to reduce the data dimension and the optimum choice of the data, will lead to a more accurate system. So considering the data mining approaches due to the nature of medical data is necessary.


Relationship between pulmonary artery acceleration time and pulmonary artery pressures in infants.
Pulmonary artery acceleration time measured by echocardiography inversely correlates with pulmonary artery pressures in adults and children older than 1 year of age. There is a paucity of data investigating this relationship in young children, particularly among preterm infants. To characterize the relationship between pulmonary artery acceleration time (PAAT) and pulmonary artery pressures in infants. Patients ≤ 1 year of age at Children's Hospital of Philadelphia between 2011 and 2017 were reviewed. Infants with congenital heart disease were excluded, except those with a patent ductus arteriosus (PDA), atrial septal defect (ASD), or ventricular septal defect (VSD). Linear regression analysis was used to assess the correlation between PAAT measured by echocardiography and systolic pulmonary artery pressure, mean pulmonary artery pressure, and indexed pulmonary vascular resistance from cardiac catheterization. Fifty-seven infants were included, of which 61% were preterm and 49% had a diagnosis of bronchopulmonary dysplasia. The median postmenstrual age and weight at catheterization were 51.1 weeks (IQR 35.8-67.9 weeks) and 4400 g (IQR 3100-6500 g), respectively. Forty-four infants (77%) had a patent ductus arteriosus (PDA). There was a weak inverse correlation between PAAT with mPAP (r = -0.35, P = 0.01), sPAP (r = -0.29, P = 0.03), and PVRi (r = -0.29, P = 0.03). There is a weak inverse relationship between PAAT and pulmonary artery pressures. This relationship is less robust in our population of infants with a high incidence of PDAs compared to previous studies in older children. Thus, PAAT may be less clinically meaningful for diagnosing pulmonary arterial hypertension in infants, particularly those with PDAs.


HL-A 27-associated arthritis.
Seventy-one of 78 patients presenting to routine rheumatology clinics with seronegative arthritis were found to possess the histocompatibility antigen HL-A 27. Four principal components to their arthritis emerged, namely: spondylitis, sacroiliitis, peripheral polyarthritis, oligoarthritis (involvement of one or two large joints). It is suggested that each of these may be influenced by separate genetic determinants. The various combinations in which these occur warrant a unified nomenclature. A small subgroup of patients with HL-A 27-associated arthritis is described in whom the diseases may be especially benign.


Psychiatric reactions to continuous traumatic stress: A Latent Profile Analysis of two Israeli samples.
Many individuals worldwide are exposed to continuous traumatic stress (CTS). However, the psychiatric sequela of CTS and the relevance of posttraumatic stress disorder (PTSD) diagnostic criteria in this situation have yet to be determined. Filling this gap, the present study assessed psychiatric reactions to CTS and the relationship between such reactions and functional impairment among two representative samples of adults exposed to ongoing shelling over 6 (n=387) and 9 years (n=468). Assessment included PTSD symptomatology (i.e., intrusion, avoidance, hyperarousal), anxiety, somatization, and depression. Profile categorization aimed to underscore variations in symptom clustering and severity, and determine whether or not a profile is dominated by PTSD symptoms. Latent Profile analyses (LPA) of sample I revealed four distinct symptoms profiles: (1) 'symptomatically resilient'; (2) 'symptomatically low-moderate'; (3) 'symptomatically moderate-high'; and (4) 'symptomatically overall high'. LPA of sample II revealed three distinct symptoms profiles: (1) 'symptomatically resilient'; (2) 'symptomatically low-moderate'; (3) "symptomatically moderate-high". Moreover, profile variation was implicated in dysfunction. Consistent with studies focusing on single trauma exposure, the findings revealed that the most prevalent profile was the symptomatically resilient, indicating that most people exposed to CTS seem to evince a scarce number of psychiatric symptoms. Moreover, reactions to CTS proved broader than the existing PTSD symptomatology. Examining symptom dominance and severity in relation to impairment and dysfunction, and clinical considerations are discussed.


Afferent pupillary defect in pineal region tumour.
A patient is described in whom an afferent pupillary defect was an early sign of a tumour in the pineal region. It is suggested that this was due to involvement of the pupillary afferent fibres between the optic tract and pretectal nucleus contralateral to the affected pupil.


One-year-old fear memories rapidly activate human fusiform gyrus.
Fast threat detection is crucial for survival. In line with such evolutionary pressure, threat-signaling fear-conditioned faces have been found to rapidly (<80 ms) activate visual brain regions including the fusiform gyrus on the conditioning day. Whether remotely fear conditioned stimuli (CS) evoke similar early processing enhancements is unknown. Here, 16 participants who underwent a differential face fear-conditioning and extinction procedure on day 1 were presented the initial CS 24 h after conditioning (Recent Recall Test) as well as 9-17 months later (Remote Recall Test) while EEG was recorded. Using a data-driven segmentation procedure of CS evoked event-related potentials, five distinct microstates were identified for both the recent and the remote memory test. To probe intracranial activity, EEG activity within each microstate was localized using low resolution electromagnetic tomography analysis (LORETA). In both the recent (41-55 and 150-191 ms) and remote (45-90 ms) recall tests, fear conditioned faces potentiated rapid activation in proximity of fusiform gyrus, even in participants unaware of the contingencies. These findings suggest that rapid processing enhancements of conditioned faces persist over time.


Important fossil source contribution to brown carbon in Beijing during winter.
Organic aerosol (OA) constitutes a substantial fraction of fine particles and affects both human health and climate. It is becoming clear that OA absorbs light substantially (hence termed Brown Carbon, BrC), adding uncertainties to global aerosol radiative forcing estimations. The few current radiative-transfer and chemical-transport models that include BrC primarily consider sources from biogenic and biomass combustion. However, radiocarbon fingerprinting here clearly indicates that light-absorbing organic carbon in winter Beijing, the capital of China, is mainly due to fossil sources, which contribute the largest part to organic carbon (OC, 67 ± 3%) and its sub-constituents (water-soluble OC, WSOC: 54 ± 4%, and water-insoluble OC, WIOC: 73 ± 3%). The dual-isotope (Δ14C/δ13C) signatures, organic molecular tracers and Beijing-tailored emission inventory identify that this fossil source is primarily from coal combustion activities in winter, especially from the residential sector. Source testing on Chinese residential coal combustion provides direct evidence that intensive coal combustion could contribute to increased light-absorptivity of ambient BrC in Beijing winter. Coal combustion is an important source to BrC in regions such as northern China, especially during the winter season. Future modeling of OA radiative forcing should consider the importance of both biomass and fossil sources.


Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials.
Beta-Adrenergic blockers have been considered relatively contraindicated in peripheral arterial disease because of the perceived risk that these drugs could worsen intermittent claudication. Therefore, we conducted a meta-analysis of available randomized controlled trials from the English-language literature to determine whether or not beta-blockers exacerbate intermittent claudication. The primary focus of this analysis was the effect of beta-blockers on exercise duration, measured as walking capacity or endurance time. Outcomes were pooled where appropriate. Of 11 eligible reports, six included 11 individual controlled treatment comparisons that provided data for an analysis of pain-free exercise capacity; no effect size was statistically significant. The pooled effect size for pain-free walking distance was -0.24 (95% confidence interval, -0.62 to 0.14), indicating no significant impairment of walking capacity compared with placebo. Only one study reported that certain beta-blockers were associated with worsening of intermittent claudication. These results strongly suggest that beta-blockers do not adversely affect walking capacity or symptoms of intermittent claudication in patients with mild to moderate peripheral arterial disease. In the absence of other contraindications, beta-blockers can probably be used safely in such patients.


Comorbidity Patterns in Patients Newly Diagnosed With Colorectal Cancer: Network-Based Study.
Patients with colorectal cancer (CRC) often present with multiple comorbidities, and many of these can affect treatment and survival. However, previous comorbidity studies primarily focused on diseases in commonly used comorbidity indices. The comorbid status of CRC patients with respect to the entire spectrum of chronic diseases has not yet been investigated. This study aimed to systematically analyze all chronic diagnoses and diseases co-occurring, using a network-based approach and large-scale administrative health data, and provide a complete picture of the comorbidity pattern in patients newly diagnosed with CRC from southwest China. In this retrospective observational study, the hospital discharge records of 678 hospitals from 2015 to 2020 in Sichuan Province, China were used to identify new CRC cases in 2020 and their history of diseases. We examined all chronic diagnoses using ICD-10 (International Classification of Diseases, 10th Revision) codes at 3 digits and focused on chronic diseases with >1% prevalence in at least one subgroup (1-sided test, P<.025), which resulted in a total of 66 chronic diseases. Phenotypic comorbidity networks were constructed across all CRC patients and different subgroups by sex, age (18-59, 60-69, 70-79, and ≥80 years), area (urban and rural), and cancer site (colon and rectum), with comorbidity as a node and linkages representing significant correlations between multiple comorbidities. A total of 29,610 new CRC cases occurred in Sichuan, China in 2020. The mean patient age at diagnosis was 65.6 (SD 12.9) years, and 75.5% (22,369/29,610) had at least one comorbidity. The most prevalent comorbidities were hypertension (8581/29,610, 29.0%; 95% CI 28.5%-29.5%), hyperplasia of the prostate (3816/17,426, 21.9%; 95% CI 21.3%-22.5%), and chronic obstructive pulmonary disease (COPD; 4199/29,610, 14.2%; 95% CI 13.8%-14.6%). The prevalence of single comorbidities was different in each subgroup in most cases. Comorbidities were closely associated, with disorders of lipoprotein metabolism and hyperplasia of the prostate mediating correlations between other comorbidities. Males and females shared 58.3% (141/242) of disease pairs, whereas male-female disparities occurred primarily in diseases coexisting with COPD, cerebrovascular diseases, atherosclerosis, heart failure, or renal failure among males and with osteoporosis or gonarthrosis among females. Urban patients generally had more comorbidities with higher prevalence and more complex disease coexistence relationships, whereas rural patients were more likely to have co-existing severe diseases, such as heart failure comorbid with the sequelae of cerebrovascular disease or COPD. Male-female and urban-rural disparities in the prevalence of single comorbidities and their complex coexistence relationships in new CRC cases were not due to simple coincidence. The results reflect clinical practice in CRC patients and emphasize the importance of measuring comorbidity patterns in terms of individual and coexisting diseases in order to better understand comorbidity patterns.


The effect of acute distal radioulnar joint laxity on outcome after volar plate fixation of distal radius fractures.
The objective of this study was to determine whether intraoperative laxity of the distal radioulnar joint (DRUJ) is associated with adverse postoperative outcomes after volar plate fixation of a distal radius fracture (DRF) and 4 weeks of immobilization. Prospective study with clinical and radiographic assessment. Level 1 trauma center. One hundred consecutive patients were treated by volar locking plate fixation at our institution for an unstable DRF from April 2007 to November 2009. Of these patients, 84 patients with a minimum follow-up of 12 months were enrolled in this study. Intraoperative DRUJ laxity was evaluated using a radioulnar stress test after fixation of DRF using volar locking plate and splint immobilization of the forearm for 1 month in patients with intraoperative DRUJ laxity. Patients were allocated to an unstable group or stable group according to the presence of intraoperative DRUJ laxity. Our primary outcome measure was disabilities of arm, shoulder, and hand score and the secondary outcome measures were wrist motion, grip strength, modified Mayo wrist score, visual analogue scale for wrist pain, and ongoing pain in the DRUJ. Nineteen of the 84 study subjects were allocated to the unstable group and 65 to the stable group. No significant differences were observed between 2 groups in wrist range of motion, grip strength, modified Mayo wrist score, disabilities of arm, shoulder, and hand score, visual analogue scale score, and ongoing pain in the DRUJ at 1 year postoperatively. In our series of patients treated with volar locking plate and immobilization of the forearm for 1 month in patients with intraoperative laxity of the DRUJ, laxity did not affect impairment, pain, or disability 1 year after fracture. However, the role of postoperative immobilization of the forearm is debatable and merits additional study. Prognostic level I.


A role for AtWRKY23 in feeding site establishment of plant-parasitic nematodes.
During the interaction between sedentary plant-parasitic nematodes and their host, complex morphological and physiological changes occur in the infected plant tissue, finally resulting in the establishment of a nematode feeding site. This cellular transformation is the result of altered plant gene expression most likely induced by proteins injected in the plant cell by the nematode. Here, we report on the identification of a WRKY transcription factor expressed during nematode infection. Using both promoter-reporter gene fusions and in situ reverse transcription-polymerase chain reaction, we could show that AtWRKY23 is expressed during the early stages of feeding site establishment. Knocking down the expression of WRKY23 resulted in lower infection of the cyst nematode Heterodera schachtii. WRKY23 is an auxin-inducible gene and in uninfected plants WRKY23 acts downstream of the Aux/IAA protein SLR/IAA14. Although auxin is known to be involved in feeding site formation, our results suggest that, during early stages, auxin-independent signals might be at play to activate the initial expression of WRKY23.


The importance of face to face, group antenatal education classes for first time mothers: A qualitative study.
To explore and understand perspectives of women expecting their first child and why they wanted to attend NHS antenatal education. This included what worries and concerns they wanted to be addressed and why this would be beneficial. It also included what they wanted their partners to be able to gain from attending classes. A longitudinal qualitative study using Template Analysis was undertaken with data collection during pregnancy and postpartum. A semi-structured topic guide was used to guide data collection, either via focus groups or one to one interviews which were audio recorded and transcribed. National Health Service Trusts providing maternity services to women for labour and birth, purposively selected to allow the perspectives of specific groups of women to be included. Women expecting their first child from one of three groups: Women from the general population aged 20 years or more, women from ethnic minority groups and young women aged 16 to 19 years. Eighty-two pregnant women participated. Three substantive themes are reported: the search for information, the functions of antenatal classes, and the specific information desired. Women wanted to attend NHS antenatal education to access trustworthy information that would reassure, increase confidence, and help them feel prepared. Women wanted to meet others in the same situation to help normalise concerns and offer the potential for ongoing relationships. Classes were seen as a way to help partners engage more fully with the transition to parenthood. Specific information required and shared by all groups was around understanding the stages of labour, managing labour, and common interventions. Access to a wide range of information increases women's anxieties about labour that women want addressed through antenatal education. However, antenatal classes serve broader functions beyond information- giving and women anticipate that attending antenatal classes will address both their own and their partners' needs. Service providers should ensure their antenatal education provision provides the information required and is structured in a way that enables women to develop relationships and supports partners' engagement in the transition to parenthood.


Aroma Identification and Classification in 18 Kinds of Teas (Camellia sinensis) by Sensory Evaluation, HS-SPME-GC-IMS/GC × GC-MS, and Chemometrics.
Tea (Camellia sinensis) is one of the most popular beverages worldwide. Many types of tea products continuously emerge in an endless stream; so, the classification of tea becomes more difficult. Aroma is a vital indicator of tea quality. The present study deals with the identification of aroma compounds in 18 different kinds of tea belonging to three typical tea varieties, including green tea, oolong tea, and black tea, using GC-IMS and GC × GC-O-MS. Moreover, the clustering of all 18 tea samples and the in depth correlation analysis between sensory evaluation and instrumental data were performed using the PCA and OPLS-DA. The results revealed that in all 18 kinds of tea, a total of 85 aroma compounds were detected by GC-IMS, whereas 318 were detected by GC × GC-O-MS. The PCA result revealed that green tea, oolong tea, and black tea could be clearly separated based on their peak areas. The OPLS-DA result showed that a total of 49 aroma compounds with VIP value > 1.0 could be considered as the potential indicators to quickly classify or verify tea types. This study not only compared the aroma differences across different types of teas, but also provided ideas for the rapid monitoring of tea quality and variety.


Individual and county level predictors of asthma related emergency department visits among children on Medicaid: A multilevel approach.
Disparities in asthma outcomes are well documented in the United States. Interventions to promote equity in asthma outcomes could target factors at the individual and community levels. The objective of this analysis was to understand the effect of individual (race, gender, age, and preventive inhaler use) and county-level factors (demographic, socioeconomic, health care, air-quality) on asthma emergency department (ED) visits among Medicaid-enrolled children. This was a retrospective cohort study of Medicaid-enrolled children with asthma in 29 states in 2009. Multilevel regression models of asthma ED visits were constructed utilizing individual-level variables (race, gender, age, and preventive inhaler use) from the Medicaid enrollment file and county-level variables reflecting population and health system characteristics from the Area Resource File (ARF). County-level measures of air quality were obtained from Environmental Protection Agency (EPA) data. The primary modifiable risk factor at the individual level was found to be the ratio of long-term controller medications to total asthma medications. County-level factors accounted for roughly 6% of the variance in the asthma ED visit risk. Increasing county-level racial segregation (OR=1.04, 95% CI=1.01-1.08) was associated with increasing risk of asthma ED visits. Greater supply of pulmonary physicians at the county level (OR=0.81, 95% CI=0.68-0.97) was associated with a reduction in risk of asthma ED visits. At the patient care level, proper use of controller medications is the factor most amenable to intervention. There is also a societal imperative to address negative social determinants, such as residential segregation.


Sound production by singing humpback whales.
Sounds from humpback whale songs were analyzed to evaluate possible mechanisms of sound production. Song sounds fell along a continuum with trains of discrete pulses at one end and continuous tonal signals at the other. This graded vocal repertoire is comparable to that seen in false killer whales [Murray et al. (1998). J. Acoust. Soc. Am. 104, 1679-1688] and human singers, indicating that all three species generate sounds by varying the tension of pneumatically driven, vibrating membranes. Patterns in the spectral content of sounds and in nonlinear sound features show that resonating air chambers may also contribute to humpback whale sound production. Collectively, these findings suggest that categorizing individual units within songs into discrete types may obscure how singers modulate song features and illustrate how production-based characterizations of vocalizations can provide new insights into how humpback whales sing.


Animal-assisted therapy: an in-depth look.
Animal-assisted therapy has gained widespread support and application over the past few decades. This article reviews the history of animal-assisted therapy; discusses its present goals and applications, including those pertinent to critical care; and notes questions requiring further research.


Transcriptome and Hormonal Analysis of Agaricus bisporus basidiomes Response to Hypomyces perniciosus Infection.
Agaricus bisporus (Lange) Imbach is the most widely cultivated mushroom in the world. Agaricus bisporus wet bubble disease is one of the most severe diseases of white button mushrooms and is caused by the fungal pathogen Hypomyces perniciosus. The pathogen causes a drastic reduction in mushroom yield due to malformation and deterioration of the basidiomes. However, the mechanism of the button mushroom's malformation development after infection with H. perniciosus remains obscure. Therefore, to reveal the mechanism of A. bisporus malformation by H. perniciosus, the interaction between the pathogen and host was investigated in this study using histopathology, physiological and transcriptomic analyses. Results show that irrespective of the growth stages of A. bisporus basidiomes infected with H. perniciosus, the host's basidiome with malformed basidiomes and enlarged mycelia and basidia indicated that the earlier the infection with H. perniciosus, the more the malformation of the basidiomes. Analyzing physiological and transcriptomic results in tandem, we concluded that H. perniciosus causes malformation development of A. bisporus mainly by affecting the level of phytohormones (N6-isopentenyladenyladenosine, cis-Zeatin and N6-(daelta2-lsopentenyl)-adenine) metabolism of the host's fruiting bodies, rather than by use of toxins. Our findings revealed the mechanism of the button mushroom's malformation development after infection with H. perniciosus, providing a reference for developing realistic approaches to control mushroom diseases. Our results further clarified the interaction between A. bisporus and H. perniciosus and identified the candidate genes for the A. bisporus wet bubble disease resistance breeding. Additionally, our work provides a valuable theoretical basis and technical support for studying the interaction between other pathogenic fungi and their fungal hosts.


Late onset CNS immune reconstitution inflammatory syndrome in an immunocompetent patient.
Immune reconstitution inflammatory syndrome (IRIS) refers to the presence of paradoxical clinical deterioration attributable to immune system recovery during highly active antiretroviral therapy (HAART). We present an immunocompetent patient with multifocal leukoencephalopathy on HAART, with central nervous system (CNS) IRIS pathology of unknown infectious etiology. CNS IRIS pathology should be suspected in patients on longstanding HAART without immune reconstitution, presenting with unexplained leukoencephalopathy.


[Effects and molecular mechanism of nicotine on odontoblasts].
To observe the effects of nicotine on the proliferation of odontoblasts and explore the possible mechanism. Odontoblasts MDPC-23 were cultured, inoculated and divided into two groups randomly. With no stimuli added for the control group, the experimental group was stimulated by 100 microg/mL nicotine. After 8 hours, 10 micromol/L BrdU was added to label cells at S stage in cell cycle. 24 hours later, odontoblasts were fixed and immunofluorescence staining was performed with specific mouse BrdU antibody. After counterstaining with propidium iodide, BrdU positive cells were arbitrarily scored microscopically by an independent estimation conducted three times, and the corresponding total cell number in the same vision were counted in both groups. BrdU positive cell rates were calculated and compared statistically. At the same time, odontoblasts MDPC-23 were cultured and stimulated by 100 microg/mL nicotine, the dynamic Ca2+ concentration inside the cytoplasm were detected immediately by a confocal laser scanning microscope. The ratio of S stage cells in the experimental group was 36.3% significantly lower than that (48.2%) in the control group. After the addition of 100 microg/mL nicotine, the Ca2+ concentration inside the cytoplasm rose rapidly, sustained at a high level for a short time and then relapsed gradually. Nicotine had inhibitory effects on the proliferation of odontoblasts MDPC-23, which might be related to the increased Ca2+ concentration in the cytoplasm.


Human suppressor factors constitutively produced by T-T cell hybridomas: functional and biochemical characterization.
We have recently developed a new method (Hybridoma 6:589, 1987) for the generation of human T-T cell hybrids. This method is based on a new selection procedure that involves cloning the hybrids in soft agar, screening by HLA-typing or appropriate functional tests and recloning by limiting dilution. T-T cell hybrids were separated from the parent line on the basis of their ability to form colonies in soft agar, whereas the parent lymphoblastoid T cell lines did not. HAT medium was not used in our selection procedure. Using this method, we have succeeded in developing human T-T cell hybrids (as determined by HLA-typing) constitutively producing B cell growth factor (BCGF) (Hybridoma 6:589, 1987) or suppressor factors. These hybrids were obtained by fusing MLC or Con A T cell blasts with cells from the Molt 4 or Jurkat lymphoblastoid T cell lines. T-T cell hybridomas, derived by fusing Con A-stimulated lymphocytes with cells from the Jurkat T cell line, produced suppressor factors inhibiting: (1) proliferative response in vitro of human peripheral blood mononuclear leukocytes to mitogens and to allogeneic cells in mixed lymphocyte culture; and (2) immunoglobulin synthesis and secretion by mononuclear leukocytes in the PWM-induced differentiation system in vitro. A suppressor factor with these inhibitory properties was also identified in supernatants of the Jurkat T cell line. These suppressor factors were ammonium sulphate precipitable, pH 2 labile, non-dialyzable and they were inactivated by treatment at 56 degrees C for 30 minutes. They exhibited a molecular weight in the range of 50,000-70,000, as determined by gel filtration, and were not gamma or alpha interferon or lymphotoxin/TNF. They did not lyse human lymphoblastoid tumor cell lines nor did they affect the viability and cell numbers of human mononuclear cells even after prolonged incubation (88 hr). They appeared to be cytostatic rather than cytotoxic molecules. The Jurkat suppressor factor is different from those produced by the hybrids on the basis of: (a) different isoelectric points; and (b) the ability of the Jurkat factor to arrest proliferation to PHA of human mononuclear cells in the S phase, whereas the 160 and 169 factors arrest proliferation at the G1 phase of the cell cycle. Certain of these suppressor factors (produced by the hybrids 153, 160, 170, and the Jurkat T cell line) also inhibited proliferative responses of mouse lymphocytes in vitro. In contrast, suppressor factors produced by the 169 and 77 hybrids did not inhibit any murine responses.


Combined effect of ampicillin, colistin and dexamethasone administered intramuscularly to dairy cows on the clinico-pathological course of E. coli-endotoxin mastitis.
The effects of a single intramuscular injection of a drug product containing ampicillin, colistin and dexamethasone, as a suspension in a diester of propylene glycol of medium-chain fatty acids, on the clinico-pathological course of experimental Escherichia coli-endotoxin mastitis was examined in 30 dairy cows. Cows were divided into five groups, six cows per group, and 24 of them were infused with E. coli endotoxin into two quarters of their udders. The drug product was injected at 25,000 IU colistin sulphate, 10.0 mg ampicillin anhydrate and 0.025 mg dexamethasone acetate.kg-1 body weight as follows: Group 2 cows, immediately post-endotoxin infusion (PEI); Group 3 cows, 2 h PEI and, Group 4 cows, 4 h PEI. Group 1 cows were not treated with the product and served as a positive (endotoxin only) control while Group 5 cows were not challenged with endotoxin and were not treated with the product. A clinical mastitis score (CMS) was developed to quantitatively assess the degree of inflammation. Blood biochemistry and hematological parameters were used to monitor the immediate effects of treatment on several conventional inflammatory markers. Milk somatic cell counts (MSCC), milk electrical conductivity and daily milk production were among the parameters used to monitor systemic and local inflammatory reactions. Administration of the drug product immediately PEI and 2 h PEI clearly nullified some of the most severe early systemic reactions to inflammation but the effect of therapy on the local inflammatory markers was not as obvious. Notewhorthy, however, were the effects of the treatment on reducing the duration of elevated quarter MSCC and the increase in the speed of return to pre-endotoxin challenge daily milk production levels.


Effects of Scaling and Root Planing on Salivary Interleukine-6 Levels in Chronic Periodontitis Patients and Glycemic Controls.
Type 2 diabetes mellitus (DM) and periodontitis have a bidirectional relationship that is well documented in many reviews and epidemiological studies. Periodontitis has been referred to as the sixth complication of diabetes mellitus. Various studies showed improvement in Interleukin-6 levels as well as metabolic parameters after non-surgical periodontal therapy in chronic periodontitis patients with type 2 DM. Objective: To evaluate the effect of scaling and root planing (SRP) on salivary levels of IL-6 and assessment of clinical parameters in CP patients with and without T2DM. We included 50 CP patients with well-controlled T2DM (Group I), and 50 CP patients without T2DM as controls (Group II) with evident clinical inflammation, ≥ 5mm probing depth (PD) and a relative attachment level (RAL) of ≥ 5mm. Following a brief medical and dental history plaque index (PI), gingival index (GI), gingival bleeding index (BI), PD, and RAL were recorded, and an unstimulated saliva was collected. Following SRP therapy, the clinical parameters and IL-6 levels were measured after seven days, 14 days, and 30 days. Intragroup and intergroup comparisons were carried out using a paired t-test and an independent t-test. The statistical significance was set at P < 0.05. Data were analyzed using computer software, Statistical Package for Social Sciences (SPSS) v. 22.0 (IBM Corp., Armonk, NY). Intergroup comparisons of IL-6 levels at different intervals showed a significantly higher reduction in Group II than in Group I (p=0.000). While the mean difference in the GI scores from baseline to 30 days was significantly higher in Group I patients (p=0.000), the difference in the mean PI (p=0.004), mean BI (p=0.000), mean PD (p=0.000) and mean RAL scores (p=0.000) were significantly higher in Group II patients. This study indicates that scaling and root planing is effective in glycemic control and also has a role to play in the level of salivary IL-6 in periodontal health and T2DM with chronic periodontitis. Elevated salivary IL-6 levels indicate periodontal inflammation which is further increased in T2DM patients. Hence, elevated IL-6 can be considered a marker of periodontal destruction.


Alcohol-mediated susceptibility to lung fibrosis is associated with group 2 innate lymphoid cells in mice.
Chronic alcohol ingestion promotes acute lung injury and impairs immune function. However, the mechanisms involved are incompletely understood. Here, we show that alcohol feeding enhances bleomycin-induced lung fibrosis and inflammation via the regulation of type 2 innate immune responses, especially by group 2 innate lymphoid cells (ILC2s). Neuroimmune interactions have emerged as critical modulators of lung inflammation. We found alcohol consumption induced the accumulation of ILC2 and reduced the production of the neuropeptide calcitonin gene-related peptide (CGRP), primarily released from sensory nerves and pulmonary neuroendocrine cells (PNECs). CGRP potently suppressed alcohol-driven type 2 cytokine signals in vivo. Vagal ganglia TRPV1+ afferents mediated immunosuppression occurs through the release of CGRP. Inactivation of the TRPV1 receptor enhanced bleomycin-induced fibrosis. In addition, mice lacking the CGRP receptor had the increased lung inflammation and fibrosis and type 2 cytokine production as well as exaggerated responses to alcohol feeding. Together, these data indicate that alcohol consumption regulates the interaction of CGRP and ILC2, which is a critical contributor of lung inflammation and fibrosis.


Excessive burden of end-state renal disease among Canadian Indians: a national survey.
Analysis of data from the Canadian National Renal Failure Register indicates that Canadian Natives are at much higher risk for end-stage renal disease (ESRD) than the Canadian population in general. Using two population estimates for the total Native population, the age-standardized incidence rate of newly registered ESRD cases between 1981 and 1986 among Natives was at least 2.5 times (and may be as high as four times) the national rate. Natives were particularly at higher risk for ESRD to diabetes, glomerulonephritis, and pyelonephritis, whereas for the other causes the risk was no different from that of other Canadians. As technologically sophisticated treatment facilities are only available in major urban centers, Native ESRD patients and their families living in remote areas of Canada are faced with major psychosocial disruptions of relocation.


Snow algae communities in Antarctica: metabolic and taxonomic composition.
Snow algae are found in snowfields across cold regions of the planet, forming highly visible red and green patches below and on the snow surface. In Antarctica, they contribute significantly to terrestrial net primary productivity due to the paucity of land plants, but our knowledge of these communities is limited. Here we provide the first description of the metabolic and species diversity of green and red snow algae communities from four locations in Ryder Bay (Adelaide Island, 68°S), Antarctic Peninsula. During the 2015 austral summer season, we collected samples to measure the metabolic composition of snow algae communities and determined the species composition of these communities using metabarcoding. Green communities were protein-rich, had a high chlorophyll content and contained many metabolites associated with nitrogen and amino acid metabolism. Red communities had a higher carotenoid content and contained more metabolites associated with carbohydrate and fatty acid metabolism. Chloromonas, Chlamydomonas and Chlorella were found in green blooms but only Chloromonas was detected in red blooms. Both communities also contained bacteria, protists and fungi. These data show the complexity and variation within snow algae communities in Antarctica and provide initial insights into the contribution they make to ecosystem functioning.


Selective inhibition of sleep related growth hormone release by Phe-4-somatostatin.
We have compared the effects of somatostatin (SS) and the somatostatin analog Phe-4-SS on nocturnal GH secretion in three normal male volunteers, 20 to 23 years of age. Subjects were studied in our sleep laboratory on 5 consecutive nights. Nights 1 and 2 were used for adaptation. On the third night (control night), all patients exhibited a typical GH peak accompanying slow-wave sleep, with maximum GH levels from 9.2 to 27 ng/ml. Insulin, glucagon and glucose levels were episodic and sleep-independent. On night 4, subjects received SS infusion at a rate of 3 micrograms/min, which inhibited GH levels consistently below 2.4 ng/ml. In two cases a post-infusion rebound of GH levels was observed. During SS infusion all three subjects showed a significant decrease in insulin levels (p less than 0.0005), followed by an immediate rebound after infusion was stopped. Glucagon levels fell significantly during infusion (p less than 0.001, p less than 0.025 and p less than 0.00025 respectively). Glucose was significantly higher than on control night in subject No. 3 (p less than 0.0005) and similar to control night in subjects 1 and 2. On the fifth night, Phe-4-SS was infused at a rate of 0.75 microgram/min. GH levels decreased significantly as compared to control night in all three subjects and remained virtually constant throughout the night. Insulin levels were diminished in subject No. 1 (p less than 0.0005), but were comparable to control values in subjects 2 and 3. Cessation of analog infusion was followed by a rebound in insulin levels in all three subjects. Glucagon values were not significantly lowered and the rebound effect was not apparent. Glucose levels were higher in response to Phe-4-SS than on control night, and fell below infusion values (p less than 0.001) after administration was discontinued. It was concluded that Phe-4-SS inhibits nocturnal secretion of GH more selectively than SS, but its effect is not more prolonged than that of SS.


Progressive Cortical Neuronal Damage and Extracranial-Intracranial Bypass Surgery in Patients with Misery Perfusion.
Misery perfusion may cause selective neuronal damage in atherosclerotic ICA or MCA disease. Bypass surgery can improve misery perfusion and may prevent neuronal damage. On the other hand, surgery conveys a risk for neuronal damage. The purpose of this retrospective study was to determine whether progression of cortical neuronal damage in surgically treated patients with misery perfusion is larger than that in surgically treated patients without misery perfusion or medically treated patients with misery perfusion. We evaluated the distribution of benzodiazepine receptors twice by using PET and 11C-labeled flumazenil in 18 surgically treated patients with atherosclerotic ICA or MCA disease (9 with misery perfusion and 9 without) and no perioperative stroke before and after bypass surgery; in 8 medically treated patients with misery perfusion and no intervening ischemic event; and in 7 healthy controls. We quantified abnormal decreases in the benzodiazepine receptors of the cerebral cortex within the MCA distribution and compared changes in the benzodiazepine receptor index among the 3 groups. The change in the benzodiazepine receptor index in surgically treated patients with misery perfusion (27.5 ± 15.6) during 7 ± 5 months was significantly larger than that in surgically treated patients without misery perfusion (-5.2 ± 9.4) during 6 ± 4 months (P < .001) and in medically treated patients with misery perfusion (3.2 ± 15.4) during 16 ± 6 months (P < .01). Progression of cortical neuronal damage in surgically treated patients with misery perfusion and no perioperative stroke may occur and may be larger than that in medically treated patients with misery perfusion and no intervening ischemic event.


Acupuncture analgesia in dentistry: an analysis of studies from the People's Republic of China.
Studies conducted on the use of acupuncture analgesia for dental procedures in the People's Republic of China have not provided sufficient evidence to indicate that acupuncture analgesia can replace conventional drugs as the preferred anesthetic. However, studies currently in progress in China and in the United States may be successful in finding ways to reduce the failure rate and in determining the operative benefits of acupuncture.


A novel electrochemical sensor based on zirconia/ordered macroporous polyaniline for ultrasensitive detection of pesticides.
A simple and mild strategy was proposed to develop a novel electrochemical sensor based on zirconia/ordered macroporous polyaniline (ZrO2/OMP) and further used for the detection of methyl parathion (MP), one of the organophosphate pesticides (OPPs). Due to the strong affinity of phosphate groups with ZrO2 and the advantages of OMP such as high catalytic activity and good conductivity, the developed sensor showed a limit of detection as low as 2.28 × 10(-10) mol L(-1) (S/N = 3) by square-wave voltammograms, and good selectivity, acceptable reproducibility and stability. Most importantly, this novel sensor was successfully applied to detect MP in real samples of apple and cabbage. It is expected that this method has potential applications in electrochemical sensing platforms with simple, sensitive, selective and fast analysis.


Whole-transcriptome analysis delineates the human placenta gene network and its associations with fetal growth.
The placenta is the principal organ regulating intrauterine growth and development, performing critical functions on behalf of the developing fetus. The delineation of functional networks and pathways driving placental processes has the potential to provide key insight into intrauterine perturbations that result in adverse birth as well as later life health outcomes. We generated the transcriptome-wide profile of 200 term human placenta using the Illumina HiSeq 2500 platform and characterized the functional placental gene network using weighted gene coexpression network analysis (WGCNA). We identified 17 placental coexpression network modules that were dominated by functional processes including growth, organ development, gas exchange and immune response. Five network modules, enriched for processes including cellular respiration, amino acid transport, hormone signaling, histone modifications and gene expression, were associated with birth weight; hub genes of all five modules (CREB3, DDX3X, DNAJC14, GRHL1 and C21orf91) were significantly associated with fetal growth restriction, and one hub gene (CREB3) was additionally associated with fetal overgrowth. In this largest RNA-Seq based transcriptome-wide profiling study of human term placenta conducted to date, we delineated a placental gene network with functional relevance to fetal growth using a network-based approach with superior scale reduction capacity. Our study findings not only implicate potential molecular mechanisms underlying fetal growth but also provide a reference placenta gene network to inform future studies investigating placental dysfunction as a route to future disease endpoints.


Adrenaline and the development of genetic hypertension.
The effects, on the development of a raised blood pressure in spontaneously hypertensive (SHR) rats, of bilateral adrenal demedullation and subcutaneous slow-release implants containing adrenaline, salbutamol and procaterol were studied. Systolic blood pressure (SBP) measurements were made, using an indirect tail-cuff method in groups of male SHR rats aged from three to 14 weeks, which were sham-operated or bilaterally adrenal demedullated under ether anaesthesia at four weeks of age. Bilateral adrenal demedullation attenuated the development of a raised blood pressure, while slow-release implants of adrenaline restored the development of hypertension in adrenal demedullated rats and this effect was abolished by concomitant treatment with the beta 2-adrenoceptor antagonist [C] 118551. Implants of salbutamol and procaterol were also effective in restoring hypertension development in adrenal demedullated rats. It is suggested that adrenaline exerts its pro-hypertensive effects via an action at beta 2-adrenoceptors; possibly those located prejunctionally which are involved in the facilitation of sympathetic neurotransmission.


Crystallization of indium tin oxide nanoparticles: from cooperative behavior to individuality.
The crystallization pathway of indium tin oxide nanoparticles during solvothermal synthesis in benzyl alcohol was investigated. The synthesis was stopped after different reaction times in the range of 1-24 h, and the structural and morphological characteristics of the products were analyzed by powder X-ray diffraction, electron microscopy, and UV/Vis spectroscopy. Interestingly, the crystallization mechanism does not proceed along a simple nucleation and growth pathway, but involves a two-step process. In the first 12 h an intermediate phase is formed, which consists of nanocrystallites 3-6 nm in size stabilized by an organic matrix. In this organic-inorganic network the nanoparticles are aligned into superstructures, but without any crystallographic orientation. After 12 h the intermediate phase is abruptly transformed into indium tin oxide nanoparticles with the bixbyite structure and with crystallite sizes of about 10-12 nm. This step is accompanied by the disappearance of the organic phase and the loss of the superstructure.


Osteoblastic cell proliferation with uniform distribution in a large scaffold using radial-flow bioreactor.
Bioreactors employing different types of in vitro physiological cell stimulation have been developed to obtain three-dimensional cultivation for tissue engineering. The aim of this study was to determine whether osteoblastic cells proliferated uniformly over a large scaffold with a diameter of 18 mm and height of 10 mm under dynamic cultivation with the radial-flow bioreactor (RFB), and thereby ascertain the potential of this system in the regeneration of jaw bone. Mouse osteoblastic cells (MC3T3-E1) were seeded onto type 1 collagen sheets. Cells were then incubated outside the reactor for 6 h to produce precultured sheets. The six precultured sheets were then placed in the RFB to fabricate the scaffolds. Cells were dynamically cultured for 1 week at 37°C, pH 7.4, dissolved oxygen 6.86 ppm, and with the culture medium circulating at 3 mL/min. As a control, static cultivation cultured in the same manner without the circulating culture medium and single cultivation in a culture dish were performed. The resulting cell proliferation and cell distribution were analyzed. After 1 week of dynamic cultivation, cells showed a fivefold and fourfold increase with uniform distribution throughout the three-dimensional scaffolds than those under the static and single cultivation as a control, respectively. These results indicate that the RFB is a promising system for three-dimensional cultivation of osteoblastic cells for treating large bone defects by tissue engineering.


Sewage Protein Information Mining: Discovery of Large Biomolecules as Biomarkers of Population and Industrial Activities.
Wastewater-based epidemiology has been revealed as a powerful approach for surveying the health and lifestyle of a population. In this context, proteins have been proposed as potential biomarkers that complement the information provided by currently available methods. However, little is known about the range of molecular species and dynamics of proteins in wastewater and the information hidden in these protein profiles is still to be uncovered. In this study, we investigated the protein composition of wastewater from 10 municipalities in Catalonia with diverse populations and industrial activities at three different times of the year. The soluble fraction of this material was analyzed using liquid chromatography high-resolution tandem mass spectrometry using a shotgun proteomics approach. The complete proteomic profile, distribution among different organisms, and semiquantitative analysis of the main constituents are described. Excreta (urine and feces) from humans, and blood and other residues from livestock were identified as the two main protein sources. Our findings provide new insights into the characterization of wastewater proteomics that allow for the proposal of specific bioindicators for wastewater-based environmental monitoring. This includes human and animal population monitoring, most notably for rodent pest control (immunoglobulins (Igs) and amylases) and livestock processing industry monitoring (albumins).


Glucagon-like peptide-2 activates beta-catenin signaling in the mouse intestinal crypt: role of insulin-like growth factor-I.
Chronic administration of glucagon-like peptide-2 (GLP-2) induces intestinal growth and crypt cell proliferation through an indirect mechanism requiring IGF-I. However, the intracellular pathways through which IGF-I mediates GLP-2-induced epithelial tropic signaling remain undefined. Because beta-catenin and Akt are important regulators of crypt cell proliferation, we hypothesized that GLP-2 activates these signaling pathways through an IGF-I-dependent mechanism. In this study, fasted mice were administered Gly(2)-GLP-2 or LR(3)-IGF-I (positive control) for 0.5-4 h. Nuclear translocation of beta-catenin in non-Paneth crypt cells was assessed by immunohistochemistry and expression of its downstream proliferative markers, c-myc and Sox9, by quantitative RT-PCR. Akt phosphorylation and activation of its targets, glycogen synthase kinase-3beta and caspase-3, were determined by Western blot. IGF-I receptor (IGF-IR) and IGF-I signaling were blocked by preadministration of NVP-AEW541 and through the use of IGF-I knockout mice, respectively. We found that GLP-2 increased beta-catenin nuclear translocation in non-Paneth crypt cells by 72 +/- 17% (P < 0.05) and increased mucosal c-myc and Sox9 mRNA expression by 90 +/- 20 and 376 +/- 170%, respectively (P < 0.05-0.01), with similar results observed with IGF-I. This effect of GLP-2 was prevented by blocking the IGF-IR as well as ablation of IGF-I signaling. GLP-2 also produced a time- and dose-dependent activation of Akt in the intestinal mucosa (P < 0.01), most notably in the epithelium. This action was reduced by IGF-IR inhibition but not IGF-I knockout. We concluded that acute administration of GLP-2 activates beta-catenin and proliferative signaling in non-Paneth murine intestinal crypt cells as well as Akt signaling in the mucosa. However, IGF-I is required only for the GLP-2-induced alterations in beta-catenin.


Fatal polyarteritis nodosa with gastrointestinal involvement in a child.
Polyarteritis nodosa (PAN) is a necrotizing angiitis that predominantly affects small- and medium-sized arteries. Polyarteritis nodosa occurs rarely during childhood. Boys and girls seem to be equally affected, with a peak at the age of 10 years. Rarely, severe and fatal gastrointestinal involvement is seen in PAN. Here, we report a 15-year-old boy with PAN, who had gastrointestinal involvement with multiple aneurysms of the hepatic and superior mesenteric arteries. This involvement could be demonstrated with conventional angiography and gastrointestinal bleeding scintigraphy. The progression of the symptoms and the decrease in the size of the aneurysms were noted after combination treatment with cyclophosphamide and prednisolone, but there was severe bleeding from small bowel, and it was taken under control by resection of jejunum. However, the patient died because of sepsis. In conclusion, severe gastrointestinal involvement in PAN is usually fatal despite aggressive therapy, as is the case in our patient.


Comparisons of Molecular Structure Generation Methods Based on Fragment Assemblies and Genetic Graphs.
The use of quantitative structure-property relationships (QSPRs) helps in predicting molecular properties for several decades, while the automatic design of new molecular structures is still emerging. The choice of algorithms to generate molecules is not obvious and is related to several factors such as the desired chemical diversity (according to an initial dataset's content) and the level of construction (the use of atoms, fragments, pattern-based methods). In this paper, we address the problem of molecular structure generation by revisiting two approaches: fragment-based methods (FMs) and genetic-based methods (GMs). We define a set of indices to compare generation methods on a specific task. New indices inform about the explored data space (coverage), compare how the data space is explored (representativeness), and quantifies the ratio of molecules satisfying requirements (generation specificity) without the use of a database composed of real chemicals as a reference. These indices were employed to compare generations of molecules fulfilling the desired property criterion, evaluated by QSPR.


Thyroid stimulating and thyrotrophin binding-inhibitory immunoglobulin activity in patients with systemic lupus erythematosus having thyroid function abnormalities.
In order to determine whether thyroid function abnormalities seen in patients with systemic lupus erythematosus (SLE) are associated with autoantibodies directed against the TSH receptor, 28 patients with SLE who demonstrated abnormal thyroid function tests were evaluated for the presence of anti-TSH receptor antibodies. Anti-TSH receptor antibody activity was evaluated by assessing cAMP production in vitro in FRTL-5 (rat thyroid) cells (TSI) and the ability of the subjects' IgG to block the binding of thyrotrophin to its receptor in vitro (TBII). Complete thyroid function tests, including TRH testing, also were performed. Ten of the 28 patients demonstrated TSI activity, ranging from 133% to 183% of control. Five patients also had evidence of TBII activity, ranging from 22% to 90% inhibition (of control TSH binding levels), with 2 patients having evidence of both types of antibodies. Neither the TSI nor TBII activity in these patients was associated with the abnormal thyroid function tests. However, there were significantly more patients with TBII activity who had elevated TSH levels (3 of 4 vs 1 of 24, p less than 0.05), suggesting a potential physiologic response to TSH receptor blockade. These results indicate that patients with SLE and thyroid function abnormalities can demonstrate TBII and TSI activity in their serum. However, these antibodies do not necessarily correlate with specific abnormalities of thyroid function.


Increased solubility of newly synthesized collagen in retinal capillary pericyte cultures by nonenzymatic glycosylation.
The effect of increasing glucose concentration on the solubility of newly synthesized collagen was studied in bovine retinal capillary pericyte (BRCP) cultures. Synchronized pericytes were labeled with [3H]-proline in media containing either 5, 10, 20 or 40 mM glucose, or 5 mM glucose and 100 micrograms/ml beta-aminopropionitrile fumarate (BAPN). The relative rate of collagen synthesis in the medium (soluble collagen) was significantly increased, and the rate in the cell layer (insoluble collagen) was decreased, by an elevated glucose concentration. The increase in collagen solubility with 20 and 40 mM glucose (over normal, 5 mM glucose) was 14 and 42%, respectively, of that obtained with BAPN. BAPN and 4-deoxypyridoxine inhibited BRCP lysyl oxidase activity, but elevated glucose concentrations did not. Increased nonenzymatic glycosylation of newly synthesized collagen was demonstrated in BRCP cultures co-labeled with L-[14C]-glucose and L-[3H]-proline. The increase in collagen solubility with elevated glucose concentrations therefore appears to be the result of the inhibition of lysyl-derived cross-link formation because of an increased nonenzymatic glycosylation of the epsilon-amino groups of lysyl residues of newly synthesized collagen in culture.


Maladaptive Laterality in Cortical Networks Related to Social Communication in Autism Spectrum Disorder.
Neuroimaging studies of individuals with autism spectrum disorders (ASDs) consistently find an aberrant pattern of reduced laterality in brain networks that support functions related to social communication and language. However, it is unclear how the underlying functional organization of these brain networks is altered in ASD individuals. We tested four models of reduced laterality in a social communication network in 70 ASD individuals (14 females) and a control group of the same number of tightly matched typically developing (TD) individuals (19 females) using high-quality resting-state fMRI data and a method of measuring patterns of functional laterality across the brain. We found that a functionally defined social communication network exhibited the typical pattern of left laterality in both groups, whereas there was a significant increase in within- relative to across-hemisphere connectivity of homotopic regions in the right hemisphere in ASD individuals. Furthermore, greater within- relative to across-hemisphere connectivity in the left hemisphere was positively correlated with a measure of verbal ability in both groups, whereas greater within- relative to across-hemisphere connectivity in the right hemisphere in ASD, but not TD, individuals was negatively correlated with the same verbal measure. Crucially, these differences in patterns of laterality were not found in two other functional networks and were specifically correlated to a measure of verbal ability but not metrics of other core components of the ASD phenotype. These results suggest that previous reports of reduced laterality in social communication regions in ASD is because of the two hemispheres functioning more independently than seen in TD individuals, with the atypical right-hemisphere network component being maladaptive.SIGNIFICANCE STATEMENT A consistent neuroimaging finding in individuals with ASD is an aberrant pattern of reduced laterality of the brain networks that support functions related to social communication and language. We tested four models of reduced laterality in a social communication network in ASD individuals and a TD control group using high-quality resting-state fMRI data. Our results suggest that reduced laterality of social communication regions in ASD may be because of the two hemispheres functioning more independently than seen in TD individuals, with atypically greater within- than across-hemisphere connectivity in the right hemisphere being maladaptive.


Extracardiac Fontan With Direct Inferior Vena Cava to Main Pulmonary Artery Connection Without Cardiopulmonary Bypass.
We report the case of a six-year-old patient who underwent an extracardiac Fontan operation including bilateral bidirectional superior cavopulmonary anastomosis and direct inferior vena cava to main pulmonary artery connection that was performed without cardiopulmonary bypass.


Probiotic and prebiotic-probiotic PEC microparticles for sustaining and enhancing intestinal probiotic growth.
The aim of the study was to develop and evaluate Polyelectrolyte complex (PEC) microparticles composing Lactobacillus Acidophilus (probiotic) and Fructo oligosaccharide-Lactobacillus Acidophilus (prebiotic-probiotic), for sustaining and enhancing intestinal growth of probiotic bacteria. Gum Karaya-Chitosan(GK-CH) was used to fabricate PEC microparticles by extrusion method. The prepared microparticles were characterized for FT-IR, DSC and particle size and evaluated for percentage yield, swelling, surface morphology, entrapment rate and further studied for influence of prebiotic over probiotic growth. The fabricated PEC microparticles composed of Probiotic and Prebiotic- Probiotic have exhibited sustainability of probiotic bacteria for 12 hrs in GIT conditions and presence of prebiotic in the preparation enhanced the probiotic cell growth. Hence, it can be concluded that PEC between GK-CH was found to be successful in sustaining cell release and presence of prebiotic was found to enhance the probiotic cell growth.


Mixed-order phase transition of the contact process near multiple junctions.
We have studied the phase transition of the contact process near a multiple junction of M semi-infinite chains by Monte Carlo simulations. As opposed to the continuous transitions of the translationally invariant (M=2) and semi-infinite (M=1) system, the local order parameter is found to be discontinuous for M>2. Furthermore, the temporal correlation length diverges algebraically as the critical point is approached, but with different exponents on the two sides of the transition. In the active phase, the estimate is compatible with the bulk value, while in the inactive phase it exceeds the bulk value and increases with M. The unusual local critical behavior is explained by a scaling theory with an irrelevant variable, which becomes dangerous in the inactive phase. Quenched spatial disorder is found to make the transition continuous in agreement with earlier renormalization group results.