Silver Nanowires Coated Nitrocellulose Paper for High-Efficiency Electromagnetic Interference Shielding.
A thin and conductive coating on an environmentally friendly polymer is imperative for protecting sensitive electronic devices. In this regard, a series of silver nanowires (AgNWs) coated nitrocellulose (NC) papers are fabricated by a simple and fast processed vacuum-assisted filtration method by varying filtrate volume to address electromagnetic interference. Their structural and EMI shielding performance is analyzed. The submicron thick and the lighter paper reveal the conductive AgNWs interwoven on the rough NC surface, making a 2D in-planar structure. Due to a strongly interconnected network, the coated paper displays an exceptional electrical conductivity of 8603 S/m. Despite having a minimum AgNW coating thickness of ∼0.69 μm and an area density of 0.041 mg/cm2, an ultrahigh EMI shielding effectiveness (SE) of about 69.4 dB (a specific EMI SE (SE/t) of 1005797 dB/cm) in the entire X-band (8-12 GHz) region is achieved. The effective material parameters, extracted using plane-wave theory, indicate that AgNWs form closed current loops resulting in magnetic losses. These AgNWs coated NC papers synthesized by a simple procedure are promising EMI shielding materials for current emerging electronic devices.


Targeting Environmental Risks to Prevent Rheumatic Disease.
Targeting environmental factors can be an important way to reduce the incidence of rheumatic diseases (RDs). Such approaches may be at population levels; furthermore, an emerging ability to identify an individual who is at very high risk for the development of a future RD can allow for personalized approaches to environmental modification for prevention. In this article, we will discuss challenges and opportunities to targeting environmental factors for the prevention of RDs.


Effects of astaxanthin on depressive and sleep symptoms: A narrative mini-review.
Major depressive disorder (MDD) is a prevalent psychiatric condition that results in persistent feelings of sadness and loss of interest, imposing a significant economic burden on health systems and society. Impaired sleep is both a symptom and a risk factor for depression. Natural astaxanthin (AST), a carotenoid primarily derived from algae and aquatic animals, possesses multiple pharmacological properties such as anti-inflammatory, anti-apoptotic, and antioxidant stress effects. Prior research suggests that AST may have antidepressant properties. This mini-review highlights the potential mechanisms by which AST can prevent depression, providing novel insights into drug research for depression treatment. Specifically, this mechanism suggests that astaxanthin may improve sleep and thus potentially aid in the treatment of depression.


Ecklonia cava polyphenol protects the liver against ethanol-induced injury in rats.
The development of alcoholic liver disease is a complex process that involves both the parenchymal and non-parenchymal cells of the liver. We examined the effect of an Ecklonia cava extract on ethanol-induced liver injury. Isolated hepatocytes and hepatic stellate cells (HSCs) were incubated with ethanol. Ecklonia cava polyphenol (ECP) was added to the cultures that had been incubated with ethanol. Male Wistar rats were fed a diet that included 0.02% or 0.2% ECP or no ECP. For a period of 3 weeks, the animals were given drinking water containing 5% ethanol and were also treated with carbon tetrachloride (CCl4) (0.1 ml/kg of body weight). In the cultured hepatocytes, the ECP treatment suppressed the ethanol-induced increase in cell death by maintaining intracellular glutathione (GSH) levels. In HSCs, ECP treatment suppressed the ethanol-induced increases in type I collagen and α-smooth muscle actin expression by maintaining intracellular levels of reactive oxygen species and GSH. We examined the effects of ECP on serum AST and ALT activity, as well as the progression of liver fibrosis in rats treated with ethanol and CCl4. ECP treatment suppressed plasma AST and ALT activities in the ethanol- and CCl4-treated rats. ECP treatment fully protected the rats against ethanol- and CCl4-induced liver injury. ECP may be a candidate for preventing ethanol-induced liver injury.


Primary dysmenorrhea with and without premenstrual syndrome: variation in quality of life over menstrual phases.
The majority of studies on quality of life (QoL) of women with menstrual disturbances have not taken menstrual cycle phase into account. We aimed to determine the size of changes in QoL score during perimenstrual week compared to those during late follicular phase in women suffering from dysmenorrhea with or without premenstrual syndrome (PMS) and also to compare the two groups. In this observational analytical study, participants were selected purposively from among single students aged 18-30 years, who were residing at university dormitories in Tabriz, Iran, and had moderate or severe dysmenorrhea. They reported quality of their life during the past week using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) at two time points, days 3-4 and 11-12, of their menstrual cycle. Among 52 participants with PMS and 64 without PMS, about half reported severe dysmenorrhea. The mean total quality score was significantly lower during perimenstrual week than during late follicular phase in both group with PMS [48 vs 79, mean difference - 31 (95% confidence interval - 37 to - 26)] and group without PMS [56 vs 78, - 1 (- 27 to - 18)]. The score was significantly lower in the group with PMS than in those without PMS during perimenstrual week [- 8 (- 13 to - 2)] but not during late follicular phase [2.1 (- 2.9 to 7.0)]. Dysmenorrhea with or without PMS significantly reduces QoL of women during perimenstrual week. The QoL is slightly lower in group with PMS during perimenstrual week but not during late follicular phase.


Outcomes of tuberculosis treatment among inpatients and outpatients in the city of São Paulo, Brazil.
To compare inpatient and outpatient treatment of tuberculosis, in terms of outcomes, in the city of São Paulo, Brazil, as well to determine which variables are most frequently associated with hospitalization. A prospective, longitudinal study carried out between January and December of 2007, at two large hospitals and at outpatient clinics, in two regions of the city of São Paulo. For inpatients, data were collected with a structured questionnaire. Additional data were obtained from the São Paulo State Department of Health Tuberculosis Database. Of the 474 patients included in the study, 166 were inpatients, and 308 were outpatients. The multivariate analysis showed that hospitalization for tuberculosis was associated with hospital/emergency room diagnosis of tuberculosis (OR = 55.42), with HIV co-infection (OR = 18.57), with retreatment (OR = 18.51), and with having previously sought treatment at another health care facility (OR = 12.32). For the inpatient and outpatient groups, the overall cure rates were 41.6% and 78.3%, respectively, compared with 30.4% and 58.5% for those who were co-infected with HIV, whereas the overall mortality rates were 29.5% and 2.6%, respectively, compared with 45.7% and 9.8% for those who were co-infected with HIV. Among inpatients, tuberculosis appears to be more severe and more difficult to diagnose, resulting in lower cure rates and higher mortality rates, than among outpatients. In addition, tuberculosis patients co-infected with HIV have less favorable outcomes.


Analysis of ischemic stroke MR images by means of brain atlases of anatomy and blood supply territories.
A method for atlas-assisted analysis of stroke magnetic resonance images that is a part of a stroke computer-assisted diagnosis system supporting rapid and quantitative checking of thrombolysis conditions is presented. Two brain atlases are used for analysis: atlas of anatomy (AA) and atlas of blood supply territories (BSTs). To map these atlases onto scans, two methods are used at present: (1) fast Talairach transformation and (2) midsagittal plane and brain's bounding box matching. After atlas-to-scan mapping, both atlases are superimposed onto the studied images and can be used to get their underlying anatomy and BSTs. To speed up the process of analysis, the system automatically analyzes entire regions occupied by the infarct and penumbra. By using both atlases, the system calculates the following values for each infarct and penumbra region: (1) names of all anatomic structures and BSTs within the region, (2) volumes of occupancy for each structure and territory, and (3) percentages of occupancy for each structure and territory. In addition, the system calculates the infarct-middle cerebral artery (MCA) territory ratio for diffusion-weighted images and the penumbra-MCA territory ratio for perfusion images. Atlas-assisted analysis is fast, and calculations take less than 10 seconds. This method potentially facilitates and speeds up stroke data analysis, as well as supports decision making.


Who Benefits From Helping? Moderators of the Association Between Informal Helping and Mortality.
While informal helping has been linked to a reduced risk of mortality, it remains unclear if this association persists across different levels of key social structural moderators. To examine whether the longitudinal association between informal helping and all-cause mortality differs by specific social structural moderators (including age, gender, race/ethnicity, wealth, income, and education) in a large, prospective, national, and diverse sample of older U.S. adults. We analyzed data from the Health and Retirement Study, a national sample of U.S. adults aged >50 (N = 9,662). Using multivariable Poisson regression, we assessed effect modification by six social structural moderators (age, gender, race/ethnicity, wealth, income, and education) for the informal helping (2006/2008) to mortality (2010-2016/2012-2018) association on the additive and multiplicative scales. Participants who reported ≥100 hr/year of informal helping (vs. 0 hr/year), had a lower mortality risk. Those who engaged in 1-49 hr/year most consistently displayed lower mortality risk across moderators, while those who engaged in 50-99 and ≥100 hr/year only showed decreased mortality risk across some moderators. When formally testing effect modification, there was evidence that the informal helping-mortality associations were stronger among women and the wealthiest. Informal helping is associated with decreased mortality. Yet, there appear to be key differences in who benefits from higher amounts of informal helping across social structural moderators. Further research is needed to evaluate how the associations between informal helping and health and well-being are patterned across key social structural moderators.


p21(Cip1) protects against oxidative stress by suppressing ER-dependent activation of mitochondrial death pathways.
Although it is well established that the cell cycle inhibitor p21 protects against genotoxic stress by preventing the replication of damaged DNA, recent studies have shown that the cytoplasmic form can also protect. It protects by delaying the loss of the antiapoptotic proteins Mcl-1 and Bcl-X(L); however, the mechanism of regulation is unknown. Utilizing hyperoxia as a model of chronic oxidative stress and DNA damage, p21 was detected in the nucleus and cytoplasm and cytoplasmic expression of p21 was sufficient for cytoprotection. p21 was enriched in a subcellular fraction containing mitochondria and endoplasmic reticulum (ER), suggesting that it may be coordinating ER and mitochondrial stress pathways. Consistent with this, p21 suppressed hyperoxic downregulation of BiP and subsequent activation of ER stress signaling, which affected Mcl-1, but not Bcl-X(L); though both inhibited hyperoxic cell death. Taken together, these data show that p21 integrates the DNA damage response with ER stress signaling, which then regulates mitochondrial death pathways during chronic genotoxic stress.


Stabilization of fluorine-contaminated soil in aluminum smelting site with biochar loaded iron-lanthanide and aluminum-lanthanide bimetallic materials.
Trivalent metals-modified-biochar (BC) has been widely used for the removal of fluorine (F) in water, but little is known about its effects on the stability and mobility of F-contaminated soil. Two types of modified-BC materials (BC-loaded iron-lanthanide (BC/Fe-La) and BC-loaded aluminum-lanthanide (BC/Al-La)) were synthesized and used for the remediation of F-contaminated soil. The forms of BC/LaxFe3x(OH)y in BC/Fe-La and BC/LaxAl3x(OH)y in BC/Al-La were identified by spectroscopy, X-ray dispersion, thermogravimetric, and pore diameter/volume analyses. Following application (4-12%, w/w) to F-contaminated soil for 30 d, water soluble fluoride (WSF) decreased significantly. The modified-BC with a 1:1:1 molar ratio (BC: Al3+ or Fe3+: La3+) were more effective than those at 1:0.5:0.5. The BC/Al-La were the most effective to stabilize F. In particular, the highest decrease in WSF (by 91.75%) was obtained with the application of 12% BC/Al-La-2, while 8% BC/Al-La-2% and 12% BC/Al-La-1 reduced the WSF by 87.58% and 90.17%, respectively; all values obtained were lower than the national standard of China (< 1.5 mg/L). In addition, the sequential extraction results showed that modified-BC promoted the transformation of the other chemical speciation to the Fe/Mn-F.


Noncoronary transradial angioplasty with coronary equipment: a less invasive technique.
As the safety and feasibility of the transradial approach for percutaneous coronary interventions have already been established by many series, we evaluate the safety and feasibility of this approach in noncoronary interventions such as renal, celiac, mesenteric, and subclavian angioplasty procedures. We present here our preliminary experience of noncoronary interventions via the transradial approach using coronary equipment with 100% technical and clinical success. Nine noncoronary interventions were performed in seven patients (five renal, two celiac, one mesenteric and subclavian angioplasty each). The advantage of this approach is that it limits arterial wall damage as well as potential distal embolization by the use of small guiding catheters and 0.014" guidewires. The only limitation of this approach for noncoronary interventions is the guiding catheter length in tall patients and the unavailability of large coronary balloons for subclavian, celiac, and renal interventions. With the miniaturization of equipment and improvements in technique, this approach will also become an excellent alternative for noncoronary interventions.


[Significance of the indices of the metabolic and immunological reorganization of lymphocytes stimulated by a specific O-antigen in acute dysentery patients].
Immunological and metabolic shifts occurring in the lymphocytes of patients with acute dysentery under the influence of specific Shigella O-antigens have been studied during the infectious process. These shifts, whose manifestation depends on the severity of the disease, have been shown to be most pronounced on week 1 of the disease, gradually subsiding by week 3. The indices characterizing these shifts can be used for the evaluation of the severity of Shigella infection and its prognosis.


Effect of Gubenfangxiao decoction on respiratory syncytial virus-induced asthma and expression of asthma susceptibility gene orosomucoid 1-like protein 3 in mice.
To investigate the effect of Guben-fangxiao decoction (GBFXD) on respiratory-syncytial-virus (RSV)-induced asthma and the expression of asthma susceptibility gene, orosomucoid 1-like protein 3 (ORMDL3) in mice. Seventy-two female BALB/c mice were randomly assigned to normal, model, GBFXD high dose, GBFXD moderate dose, GBFXD low dose and montelukast groups. An asthma model was induced via intraperitoneal injection and aerosol inhalation of ovalbumin (OVA) and repeated intranasal instillation of RSV in all mice, except those in the normal group. All treatments were administered at the first onset of asthma (within 8 weeks of model establishment) and the mice were euthanized after 28 days of treatment. The levels of transforming growth factor-β (TGF-β) and interleukin-6 (IL-6) in bronchoalveolar lavacie fluid (BALF) of the mice were measured and the expression of asthma susceptibility gene ORMDL3 in lung tissue was determined using real-time polymerase chain reaction (RT-PCR) and western blotting. Expression of ORMDL3 and levels of TGF-β and IL-6 were significantly higher in the model group (P < 0.05, P < 0.01) compared with the normal mice. Levels of ORMDL3, TGF-β and IL-6 were significantly lower in all three GBFXD treated groups (P < 0.05) compared with the model group. However, the levels in the GBFXD treatment groups did not differ significantly from the montelukast group. GBFXD had a therapeutic effect in this experimental model. The functional mechanism of GBFXD may involve multiple factors, including alleviation of airway inflammation, down-regulation of asthma susceptibility gene ORMDL3 and inhibition of airway remodeling.


Comparison of atrial fibrillation ablation using cryoballoon versus radiofrequency in patients with left common pulmonary veins: mid-term follow-up results.
Cryoballoon (CB) and radiofrequency (RF) ablation techniques have similar outcomes for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). However, there is limited data about the impact of different ablation strategies in patients with left common pulmonary vein (LCPV). Our aim was to compare the safety and efficacy of RF and CB ablation in AF patients with LCPV. One hundred and twenty-seven (n = 80 CB and n = 47 RF) AF patients with LCPV detected by preprocedural computerized tomography (CT) were included in the study. Ostial dimensions and trunk distance were measured in all patients. Atrial tachyarrhythmia (ATa) recurrence was defined as detection of AF, atrial flutter, or atrial tachycardia (≥ 30 s) after a 3-month blanking period. There was no significant difference in acute procedural success rates for PVI (97.5% in CB and 97.9% in RF, respectively, P = 0.953) and complication rates were similar between the groups (6 (7.5%) in CB and 4 (8.5%) in RF, respectively, P = 1.000). During a median follow-up of 20.7 (4.8-50.2) months for CB and 20.5 (6.2-36.0) months for RF, ATa recurrence was 35.0% and 38.2%, respectively (P = 0.777). Multivariate analysis did not reveal any of the morphologic parameters of LCPV as a significant predictor of ATa recurrence. Our findings demonstrated that both CB and RF ablation techniques have similar efficacy and safety in AF patients with LCPV during the mid-term follow-up.


Systemic hypertension in diabetes mellitus.
Hypertension occurs more frequently in diabetics and markedly exacerbates the vascular morbidity and mortality resulting from this metabolic disorder. However, the etiology of hypertension in diabetics remains poorly understood. Like aging persons, diabetics have increased systemic resistance and a probable reduction in baroreceptor sensitivity. They also have an expanded total body sodium pool and a tendency to lower levels of plasma renin activity. Some of these factors suggest that a subtle calcium deficiency could also be of etiologic importance.


Effect of peripheral nerve injury on cGMP and nitric oxide synthase levels in rat dorsal root ganglia: time course and coexistence.
Using the indirect immunofluorescence method, the distribution of cyclic GMP (cGMP) and nitric oxide synthase (NOS) was investigated in lumbar 5 dorsal root ganglia (DRGs) of untreated rats 1, 3 and 7 days following sciatic nerve section (axotomy). Untreated and axotomized (7 days) rats were also studied after perfusion with the NO donor sodium nitroprusside (SNP). Moreover, rats were injected with carrageenan lambda into the unilateral hindpaw and studied after 6 h, 1 day or 2 days. An increase in the number of cGMP-positive satellite cell profiles was found in axotomized DRGs at 3 days with lower numbers after 7 days. In contrast, no change in cGMP-like immunoreactivity (LI) in satellite cell profiles was detected 1 day after axotomy or 6h, 1 day or 2 days after inflammation, as compared to controls. Axotomy induced a marked increase in the percentage of NOS-immunoreactive (IR) neuron profiles in the ipsilateral DRGs as follows: 3.0% at 1 day, 15% at 3 days and 25% at 7 days, whereas no significant change was found in the expression of NOS-LI in the inflamed DRGs as compared to untreated DRGs. Between 15 and 20% of all NOS-positive neuron profiles were surrounded by, or in partial contact with, cGMP-IR satellite cells in controls 1 and 3 days after axotomy, whereas the corresponding figure was around 5% after 7 days. After SNP perfusion 60-70% of all DRG neuron profiles were partly or totally associated with cGMP-positive satellite cell profiles, with no significant difference between untreated and axotomized ganglia. The nerve injury-induced, parallel upregulation of NOS in DRG neurons and cGMP in satellite cells in the initial phase after axotomy suggests an involvement of NO as a signalling molecule between neurons and satellite cells in DRGs, especially after peripheral nerve injury, perhaps exerting a survival effect as recently proposed by Thippeswamy and Morris (1997).


Keeping a lid on calcium uptake.
Biochemical assays reveal how three proteins fit together to form the channel that controls the flow of calcium ions into mitochondria.


Incidence and pathophysiology of hypercalcemia.
Hypercalcemia occurs for various reasons in patients with malignant diseases. Most of these patients show a relative increase in bone resorption over bone formation. Increased renal tubular calcium reabsorption is also important for maintaining hypercalcemia in the majority of patients. Calcium absorption from the gut is usually decreased. In a few patients, fixed impairment of glomerular filtration contributes to hypercalcemia. Because the pathophysiology of hypercalcemia is heterogeneous, it may be considered as three separate syndromes: the humoral hypercalcemia of malignancy caused by systemic mediators; the hypercalcemia associated with localized osteolytic disease; and the hypercalcemia associated with myeloma and related hematologic malignancies. Increased bone resorption is a key feature in each of these syndromes. In malignant disease, bone resorption is enhanced because osteoclast activity is increased by the production of humoral mediators. These mediators are often produced by the tumor cells but are also produced by normal host cells that have been activated by the presence of the tumor. some of these mediators of hypercalcemia are systemic factors, but some act only locally. They include parathyroid hormone-related protein, transforming growth factor alpha, lymphotoxin, tumor necrosis factor, interleukin-1 alpha and 1,25-dihydroxyvitamin D.


Temperature and humidity of the Dräger Cato anesthetic machine circuit.
The Dräger Cato anesthetic machine (Dräger, Lübeck, Germany) effectively humidifies and warms anesthetic gases, because it has a built-in hotplate to heat the breathing system, and expired gas passes through the CO2 absorbent three times during one breath. In the present study, we measured the temperature and absolute humidity (AH) of the anesthetic circuit in the Dräger Cato machine with and without heat moisture exchangers (HME), and compared them with those in another anesthetic machine, the Aestiva/5 (Datex-Ohmeda, Helsinki, Finland). Forty-eight adult patients were randomly assigned to one of eight groups according to the anesthetic machine, fresh gas flow (FGF), and the use of HME (n = 6 each): Cato 0.51 x min(-1) without HME (group 1), Cato 1.01 x min(-1) without HME (group 2), Cato 0.51 x min(-1) with HME (group 3), Cato 1.01 x min(-1) with HME (group 4), Aestiva 0.51 x min(-1) without HME (group 5), Aestiva 1.01 x min(-1) without HME (group 6), Aestiva 0.51 x min(-1) with HME (group 7), and Aestiva 1.01 x min(-1) with HME (group 8). The temperature and AH of the anesthetic gases were measured with a Moiscope (S.K.I. Net, Tokyo, Japan), which was placed between the endotracheal tube and the Y-piece of the anesthetic circuit. The HME was placed between the Moiscope and the Y-piece of the anesthetic circuit. The temperature and AH of the anesthetic gases were measured at 5, 10, and 15 min and then every 15 min up to 150 min after tracheal intubation. Among the groups without HME (groups 1, 2, 5, and 6), the inspired temperatures and AH in groups 1 and 2 were significantly higher than those in groups 5 and 6 at all times during the study period (P < 0.01-0.001). The inspired temperatures and AH of the groups with HME (groups 3, 4, 7, and 8), were significantly higher than those in groups 2, 5, and 6 (P < 0.01-0.001). Among the groups with HME, the AH in group 3 was significantly higher than that in group 8 until the final study period. The present study indicates that the Dräger Cato machine was more effective in warming and humidifying respiratory gas than the Aestiva/5, and that Aestiva/5 without HME does not reach the optimal temperature and humidity ranges, even if minimal flow anesthesia (0.51 x min(-1)) is performed.


Inhibition of Rous sarcoma virus assembly by treatment with 2',5' adenosine nucleotides.
We have investigated the influence of 2',5' adenosine nucleotides on the replication and transformation of cells by Rous sarcoma virus (RSV). Treatment with the nucleotides ppp2',5'A4 and 2',5'A4 causes a striking reduction (50-fold) in the yield of infectious progeny virus, while ppp2',5A2 and 2',5'A3 had virtually no effect. The reduction in infectivity seen with 2',5'A4 nucleotides is paralleled by a smaller but significant (three- to four-fold) reduction in the amount of particles released as measured by reverse transcriptase activity and levels of viral structural proteins. The reduced infectivity of released particles is not due to viral RNA being missing since the amount of genomic RNA in particles from 2',5'A4-treated cultures was likewise only reduced by a factor of 2-3. Pulse-chase radioactive label experiments showed that processing of both viral group-specific antigens (gag) and viral envelope glycoprotein (env) gene products was completely normal in nucleotide-treated cultures, but that the rate of appearance of viral proteins in mature virus in the culture supernatants was reduced by a factor of about 3-4. Taken together, the data show that assembly of viral structural proteins into virions which can be released into the medium is slowed, and that assembly of virus particles with reduced infectivity follows upon nucleotide treatment. This inhibition of infectious virus production takes place without significant toxic effects on the cell; host protein synthesis is only 20% inhibited. There is also no significant effect on the secretory ability of the cells as measured by total protein release into the medium or release of fibronectin. The transformed cell phenotype was also subtly affected by 2',5'A4, but not by other oligomers. Plasminogen activator protease activity was sharply reduced upon treatment, while other typical features of RSV-transformed cells such as elevated hexose transport, and pp60src-associated protein phosphokinase activity, were little affected.


Campylocarpon fasciculare (Nectriaceae, Sordariomycetes); Novel Emergence of Black-Foot Causing Pathogen on Young Grapevines in China.
The black-foot disease of grapevine is one of the most destructive diseases in viticulture and it is caused by a complex of soil-borne fungi. This study aimed to identify the species associated with black-foot disease in young grapevines in vineyards of China. Fungal isolates were identified as Campylocarpon fasciculare, based on both morphological and multi-locus phylogenetic analysis of ITS, tef1-α and ß-tubulin sequence data. For the first time in China, we report Campylocarpon fasciculare associated with symptomatic young grapevines. Koch's postulates were performed on Vitis vinifera cv. Summer Black (SB) in a greenhouse and to confirm the pathogenicity on grapevines. This work improves the knowledge of black-foot disease in Chinese vineyards and will be helpful to growers in their decisions regarding vinicultural practices, planting and disease management.


Conventional, confocal and two-photon fluorescence microscopy investigations of polymer-supported oxygen sensors.
Luminescence-based, polymer-supported oxygen sensors, particularly those based on platinum group complexes, continue to be of analytical importance. Commercial applications range from the macroscopic (e.g. aerodynamic investigations in wind tunnels, monitoring of oxygen concentration during fermentation, and measurement of biological oxygen demand) to the microscopic (e.g. imaging of oxygen in blood, tissue, cells and other biological samples). Problems hindering the design of improved oxygen sensors include non-linear Stern-Volmer calibration plots and the multi-exponentiality of measured lifetime decays, both of which are attributed primarily to heterogeneity of the sensor molecule in the polymer support matrix. Conventional, confocal and two-photon fluorescence microscopy have proven to be invaluable tools with which the microscale heterogeneity and response of luminescence-based oxygen sensors can be investigated and compared to the macroscopic response. Results obtained for three ruthenium(II) alpha-diimine complexes in polydimethylsiloxane polymer supports indicate the presence of unquenched microcrystals within the polymer matrix that probably degrade oxygen quenching sensitivity and linearity of the Stern-Volmer quenching plot. Two-photon fluorescence microscopy proved most useful for imaging microcrystals within sensor films, and conventional microscopy allowed direct comparison between microscopic and macroscopic sensor response. The implications of the results in the rational design and mass production of luminescence-based oxygen sensors are significant.


Post-operative substrate utilisation and gas exchange using two different TPN-systems: glucose versus fat.
Twenty patients were studied over the first 4 post-operative days following abdominal aortic surgery. Ten patients had 93% of their non-protein energy as glucose and insulin was given to keep blood glucose below 10 mmol/l. The other 10 patients had 80% of non-protein energy as fat (Intralipid). Amino acids corresponding to 12 g of nitrogen were given in both groups. Gas exchange, nitrogen balance, phosphate balance, vanillylmandelic acid (VMA) excretion, 1- and 3-methylhistidine in urine, acute phase proteins, immunoglobulins and albumin were followed. Substrate utilisation was calculated from indirect calorimetry data and nitrogen excretion. Metabolism in the early post-operative phase was found to adapt to the nutrition regimen given even though the composition was extreme either in fat or carbohydrate content. The glucose-insulin regimen had a better nitrogen sparing effect and based on the difference in 3-methylhistidine excretion it is suggested that mainly protein muscle benefitted from this. Regardless of the TPN-regimen given, those patients whose RQ deviated the most from the average in their group had the highest nitrogen excretion. The two groups showed no differences in plasma proteins and catecholamine excretion.


Longitudinal follow-up study of 11 patients with pulmonary lymphangioleiomyomatosis: diverse clinical courses of LAM allow some patients to be treated without anti-hormone therapy.
The purpose of this study is to clarify the existing issues on the clinical diversity, natural history, and mode of disease progression of pulmonary lymphangioleiomyomatosis (LAM). Eleven patients with LAM were reviewed retrospectively with special reference to serial changes in pulmonary function and radiological findings during the course of their disease, treatment, and outcome. All patients were female with a mean age of 33.8 years at presentation and the observation period ranged from 2.1 to 20.8 years (mean 7.4 years). Four of six patients, treated with anti-hormone therapy, presented with exertional dyspnoea, marked airflow limitation (forced expiratory volume in 1 s/forced vital capacity, 23-38%), and severely impaired diffusing capacity (%DLCO, 21.4-36% of the predicted). The remaining two patients showed only a decreased diffusing capacity (70.6% and 59.4% of the predicted) which rapidly deteriorated with subsequent development of airflow limitation. Repeated chest computed tomographic (CT) examinations revealed increasing numbers of cysts with simultaneous loss of normal lung parenchyma in these two patients. In contrast, the five patients who received no anti-hormone therapy had no respiratory symptoms aside from pneumothorax at onset. Remarkable differences were noted, with pulmonary function being well maintained and slow progression of cystic changes on CT being observed in the latter group. Diverse clinical courses observed in patients with pulmonary LAM can be well delineated and assessed by periodic examinations including pulmonary function tests and chest CT imaging. Anti-hormone therapy is not always necessary for a certain group of LAM patients and they appear to have a stable course and favourable outcomes without anti-hormone treatment.


Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study.
The aim of this retrospective review was to compare the efficacy and safety of the atezolizumab plus carboplatin and nab-paclitaxel regimen versus the carboplatin and nab-paclitaxel regimen as front-line management for treatment-naïve, metastatic nonsquamous programmed death-ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) in a selected population. Consecutive patients with untreated, metastatic nonsquamous PD-L1-positive NSCLC who initially received the atezolizumab plus carboplatin and nab-paclitaxel (ACN) regimen or carboplatin and nab-paclitaxel (CN) regimen were retrospectively identified in two medical institutions from 2017 to 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS); secondary end point was the rate of key adverse events (AEs). In sum, 171 patients were retrospectively analysed, 47 of whom were excluded according to the criteria used in this study, leaving 124 patients (ACN: n = 60, median age 64 years [range 46-75]; CN: n = 64, 63 years [47-72]). The median duration of follow-up was 27 months [range 1-37]. At the final follow-up, the median OS was 19.9 months (95% confidence interval [CI], 16.3-22.5) in the ACN group vs. 14.8 months (95% CI 12.5-17.2) in the CN group (hazard ratio [HR] 0.51, 95% CI 0.33-0.77; p = 0.001). A marked distinction in the median PFS was seen (8.5 months [95% CI 6.7-9.4] in the ACN group vs. in the CN group [5.1 months [95% CI 3.6-6.8; HR 0.60; 95% CI 0.38-0.95; p = 0.005]). The rates of the key AEs (neutropenia and anaemia) were greater in the ACN group than in the CN group (all p < 0.05), but these AEs were manageable. Among selected populations of individuals with treatment-naïve, metastatic nonsquamous PD-L1-positive NSCLC, atezolizumab combined with carboplatin and nab-paclitaxel chemotherapy might have encouraging anticancer activity, with a tolerable safety profile.


Granular cell myoblastoma of the bronchus. Case report and literature review.
A case of multiple granular cell myoblastomas of the tracheobronchial tree is presented. The patient is well 32 months following endobronchial removal. Only 46 cases of solitary and two cases of multiple lesions of the tracheobronchial tree have been described in the literature. These lesions occur with equal frequency in men and women; at a median age of 38 years; more frequently on the right than on the left; and most commonly with cough as the presenting symptom. Most patients have been treated with major surgical resections, but conservative endobronchial removal may be effective therapy.


Cloning, expression and evaluation of the efficacy of a recombinant Baylisascaris schroederi Bs-Ag3 antigen in mice.
The gene Bs-Ag3 enconding a antigen of 37kDa from Baylisascaris schroederi (giant panda isolates), as well as the recombinant Bs-Ag3, obtained by cloning and expression of the Bs-Ag3 gene in heterologous host Escherichia coli BL-21 (DE3), were used to evaluate their ability to induce immune protective responses in BALB/c mice against L3-challenge infection in a mouse-B. schroederi model. There was a significant reduction (62.91%) of mice vaccinated with rBs-Ag3 coupled with Freund's complete adjuvant (FCA) in recovery of challenged B. schroederi L3 compared with either controls or mice vaccinated with FCA alone. Our data indicate recombinant Bs-Ag3 may be a potential target as a vaccine antigen for giant panda ascariasis.


Long-term prognostic value of elevated heart rate one year after heart transplantation.
Elevated heart rate (HR) is associated with adverse cardiovascular outcome in the general population and in patients with cardiovascular disease. Elevated HR due to graft denervation is often found in heart transplantation (HTx) patients; the effect on graft survival and vasculopathy is unclear. Thus, the aim of this study was to evaluate the role of elevated HR at 12 months post-HTx and its power to predict HTx long-term outcome. We evaluated retrospectively a prospective database of 312 patients undergoing HTx at two centers. HR was registered at 12 months post-HTx. The median HR was used as a cutoff point. Cox regression analysis was performed with variables known to be clinically relevant to mortality and those selected from the univariate analysis. During a mean follow-up of 5.5 ± 2.8 years there were 58 deaths (19%). Patients with a HR ≥ 90 bpm (median HR) at 12 months had an increased risk for all-cause mortality (Hazard Ratio=2.4, 95% CI 1.2 to 4.5, p=0.009) and mortality related to coronary allograft vasculopathy (CAV) (Hazard Ratio=3.0, 95% CI 1.25-7.14, p=0.01). Multivariate analysis showed that a HR ≥ 90 bpm independently predicted mortality (HR 3.2, 95% CI 1.4-7.1, p=0.004). Elevated HR measured at 12 months after HTx is an independent predictor of all-cause mortality in HTx recipients. A HR ≥ 90 bpm identifies a group of patients at high risk of death and CAV-related mortality at mid- to long-term.


Analysis of growth plate abnormalities following intraosseous infusion through the proximal tibial epiphysis in pigs.
Intraosseous infusion has become an increasingly popular technique for vascular access in critically ill or injured children. Continuing acceptance of this procedure by physicians and possibly by prehospital personnel may lead to inadvertent placement through the immature growth plate. In our study, we intentionally penetrated the epiphyseal plate with the intraosseous needle and infused fluids in order to observe what complications, if any, might arise from this procedure. Twenty pigs 3 to 4 weeks old had a bone marrow aspiration needle introduced into the medullary cavity through the tibial epiphysis under fluoroscopic visualization. Sodium bicarbonate at 2 mEq/kg (n = 10) or 0.9 normal saline at 2 mL/kg (n = 10) was infused through the intraosseous needle. Radiographs of the involved growth plates were taken at two months and six months after infusion. No growth disturbances or growth plate abnormalities were detected clinically or radiographically through the rapid growth phase of the porcine tibia. Therefore, we believe that intraosseous infusion is a safe method of alternative vascular access associated with no significant growth defects despite injury to the developing growth plate from placement and infusion.


Nomogram for Predicting Early Mortality after Umbilical Cord Blood Transplantation in Children with Inborn Errors of Immunity.
Pediatric patients with inborn errors of immunity (IEI) undergoing umbilical cord blood transplantation (UCBT) are at risk of early mortality. Our aim was to develop and validate a prediction model for early mortality after UCBT in pediatric IEI patients based on pretransplant factors. Data from 230 pediatric IEI patients who received their first UCBT between 2014 and 2021 at a single center were analyzed retrospectively. Data from 2014-2019 and 2020-2021 were used as training and validation sets, respectively. The primary outcome of interest was early mortality. Machine learning algorithms were used to identify risk factors associated with early mortality and to build predictive models. The model with the best performance was visualized using a nomogram. Discriminative ability was measured using the area under the curve (AUC) and decision curve analysis. Fifty days was determined as the cutoff for distinguishing early mortality in pediatric IEI patients undergoing UCBT. Of the 230 patients, 43 (18.7%) suffered early mortality. Multivariate logistic regression with pretransplant albumin, CD4 (absolute count), elevated C-reactive protein, and medical history of sepsis showed good discriminant AUC values of 0.7385 (95% CI, 0.5824-0.8945) and 0.827 (95% CI, 0.7409-0.9132) in predicting early mortality in the validation and training sets, respectively. The sensitivity and specificity were 0.5385 and 0.8154 for validation and 0.7667 and 0.7705 for training, respectively. The final model yielded net benefits across a reasonable range of risk thresholds. The developed nomogram can predict early mortality in pediatric IEI patients undergoing UCBT.


A data-driven examination of which patients follow trial protocol.
Protocol adherence in behavioral intervention clinical trials is critical to trial success. There is increasing interest in understanding which patients are more likely to adhere to trial protocols. The objective of this study was to demonstrate the use of a data-driven approach to explore patient characteristics associated with the lowest and highest rates of adherence in three trials assessing interventions targeting behaviors related to lifestyle and risk for cardiovascular disease. Each trial included a common set of baseline variables. Model-based recursive partitioning (MoB) was applied in each trial to identify participant characteristics of subgroups characterized by these baseline variables with differences in protocol adherence. Bootstrap resampling was conducted to provide optimism-corrected c-statistics of the final solutions. In the three trials, rates of protocol adherence varied from 56.9% to 87.5%. Evaluation of heterogeneity of protocol adherence via MoB in each trial resulted in trees with 2-4 subgroups based on splits of 1-3 variables. In two of the three trials, the first split was based on pain in the past week, and those reporting lower pain were less likely to be adherent. In one of these trials, the second and third splits were based on education and employment, where those with lower education levels and who were employed were less likely to be adherent. In the third trial, the two splits were based on smoking status and then marriage status, where smokers who were married were least likely to be adherent. Optimism-corrected c-statistics ranged from 0.54 to 0.63. Model-based recursive partitioning can be a useful approach to explore heterogeneity in protocol adherence in behavioral intervention trials. An important next step would be to assess whether patterns hold in other similar studies and samples. Identifying subgroups who are less likely to be adherent to an intervention can help inform modifications to the intervention to help tailor the intervention to these subgroups and increase future uptake and impact. ClinicalTrials.gov identifiers: NCT01828567, NCT02360293, and NCT01838226.


Evaluation of sleep habits, sleep chronotype, and quality of life in children with drug-resistant epilepsy in Turkey.
Drug-resistant epilepsy (DRE) is a condition that affects sleep habits and the quality of life of children unfavorably. The aim of our study was to evaluate the relationship of sleep habits and sleep chronotype with the quality of life and behavioral problems in children with DRE. In our study, 2-11-year-old children, who were either healthy or diagnosed with DRE, were evaluated. A sociodemographic data form was filled out to evaluate the general characteristics of children. The Children's Sleep Habits Questionnaire (CSHQ) and the Children's Chronotype Questionnaire (CCTQ) for sleep habits, the Pediatric Quality of Life Inventory (PedsQL) for the quality of life, and the Aberrant Behavior Checklist (ABC) for behavioral problems were filled out through face-to-face interviews with parents. Thirty children with DRE and 31 healthy children were included in our study. Statistically significant differences were found in children with DRE compared to the control group in terms of the total and the subscale scores of CSHQ, including sleep onset delay, sleep duration, sleep anxiety, parasomnias, and sleep-disordered breathing (p < 0.001). There were no significant differences between the groups in terms of CCTQ total scores and sleep patterns (p > 0.05). Significant differences were found in PedsQL total and subscale scores, and ABC scores in children with DRE compared to the control group (p < 0.001). Children's Sleep Habits Questionnaire, PedsQL, and ABC scores were significantly correlated with each other in children with DRE. Our results have shown that sleep habits and the quality of life are poor in children with DRE. Our study has shown that sleep disturbances, quality of life, and behavioral problems are strongly associated with each other in DRE. The recognition and appropriate treatment of sleep disturbances are important for improving the quality of life in children with DRE.


Prosodic clues to syntactic processing--a PET and ERP study.
Syntactic processing of spoken speech often involves prosodic clues processing. In the present PET and ERP study, subjects listened to phrases in which different prosodic segmentation dramatically changed the meaning of the phrase. In the contrast of segmented vs. non-segmented phrases, PET data revealed activation in the right dorsolateral prefrontal cortex and in the right cerebellum. These brain structures, therefore, might be part of the syntactic analysis network involved in prosodic segmentation and pitch processing. ERP results revealed frontal negativity that was sensitive to the position of the segmenting pause, possibly reflecting prosody-based semantic prediction. The present results are discussed in the context of their relation to brain networks of emotions, prosody, and syntax perception.


The role of SYNTAX score in decision-making for preoperative carotid artery screening in patients undergoing coronary artery bypass surgery.
The coexistence of coronary artery disease (CAD) in patients undergoing coronary artery bypass surgery (CABG) is a risk factor for stroke and death. The aim of this study is to evaluate the potential of the SYNTAX score (SXscore) for predicting carotid stenosis in patients undergoing CABG. We retrospectively reviewed 291 patients (225 males, mean age 60.5 ± 8.5 years) who underwent CABG in a single center in 2014 and were screened for carotid artery preoperatively. The total SXscore was obtained by scoring every luminal narrowing greater than 50% in coronary vessels larger than 1.5 mm using the SXscore algorithm. Correlations between the severity of carotid stenosis and SXscore were analyzed. As the degree of carotid artery stenosis increases (≤%50; ≥%50 vs ≥%70), the mean SXscore (19.06 ± 7.72, P > 0,05; 28.40 ± 6.89, P < 0,01; 31.02 ± 7.04, P < 0.01, respectively) were found to increase. Receiver operating characteristic analysis revealed a cut-off point of 27 or more in SXscore according to the presence of carotid stenosis greater than or equal to %70. The risk of existence of significant carotid stenosis was 58-fold greater in cases with SXscore greater than or equal to 27. In cases with SXscore greater than or equal to 27, the risk of existence of significant carotid stenosis was 58-fold greater with a confidence interval of 95%. Moreover, the presence of left main CAD was associated with the severity of carotid stenosis (<50% carotid stenosis, P > 0.05; ≥%50, P = 0.001; and ≥70, P = 0.001). This study suggests that the presence of left main coronary artery disease or SXscore greater than or equal to 27 should require preoperative carotid screening in patients undergoing CABG, regardless of the presence of risk factors.


Using inverse electrocardiography to image myocardial infarction--reflecting on the 2007 PhysioNet/Computers in Cardiology Challenge.
The goal of the 2007 PhysioNet/Computers in Cardiology Challenge was to try to establish how well it is possible to characterize the location and extent of old myocardial infarcts using electrocardiographic evidence supplemented by anatomical imaging information. A brief overview of the challenge and how different challengers approached the competition is provided, followed by detailed response of the first author to integrate electrophysiologic and anatomical data. The first author used the provided 120-electrode body-surface potential mapping data and magnetic resonance imaging heart and torso images to calculate epicardial potentials on customized ventricular geometries. A method was developed to define the location and extent of scar tissue based on the morphology of computed epicardial electrograms. Negative Q-wave deflection followed by R-wave on the left ventricular surface seemed to correspond with the location of the scar as determined by the gadolinium-enhanced magnetic resonance imaging gold standard in the supplied data sets. The method shows promising results as a noninvasive imaging tool to quantitatively characterize chronic infarcts and warrants further investigation on a larger patient data set.


In vitro activity of oral cephalosporins against pediatric isolates of Streptococcus pneumoniae non-susceptible to penicillin, amoxicillin or erythromycin.
The aim of this study was to evaluate the effects of penicillin, amoxicillin or erythromycin resistance on the in vitro activity of oral cephalosporins against Streptococcus pneumoniae pediatric isolates. A total of 282 pediatric isolates received during 2005 in the Spanish Reference Pneumococcal Laboratory were tested by agar dilution: 104 strains were penicillin-susceptible, 72 intermediate, and 106 resistant. Serotypes 9 and 14 were the most troublesome with <10% susceptibility to oral cephalosporins. Cefditoren exhibited the highest intrinsic activity against penicillin/amoxicillin-resistant pneumococci, with MIC(90s )of 0.5 microg/ml, followed by cefotaxime (2 microg/ml), cefpodoxime (4 microg/ml), cefuroxime (16 microg/ml), and cefaclor/cefixime (>or= 32 microg/ml), with 0% susceptibility to cefaclor, cefuroxime and cefpodoxime. Cefditoren 0.5 microg/ml inhibited 95.3%, 95.5%, and 98.6% of penicillin-, amoxicillin-, and erythromycin-resistant isolates, respectively. Susceptibility to oral cephalosporins shifted from >90% in penicillin-susceptible isolates to approximately 38% for cefuroxime/cefpodoxime and approximately 7% for cefaclor in penicillin-intermediate, and to 0% in resistant isolates. Despite the different in vitro activity of oral cephalosporins, full resistance to penicillin or amoxicillin implied lack of susceptibility to all oral cephalosporins with defined CLSI breakpoints, rendering them inadequate as empirical treatment in countries with a high prevalence of penicillin resistance.


Remarkable stability of an instability-prone lentiviral vector plasmid in Escherichia coli Stbl3.
Large-scale production of plasmid DNA to prepare therapeutic gene vectors or DNA-based vaccines requires a suitable bacterial host, which can stably maintain the plasmid DNA during industrial cultivation. Plasmid loss during bacterial cell divisions and structural changes in the plasmid DNA can dramatically reduce the yield of the desired recombinant plasmid DNA. While generating an HIV-based gene vector containing a bicistronic expression cassette 5'-Olig2cDNA-IRES-dsRed2-3', we encountered plasmid DNA instability, which occurred in homologous recombination deficient recA1 Escherichia coli strain Stbl2 specifically during large-scale bacterial cultivation. Unexpectedly, the new recombinant plasmid was structurally changed or completely lost in 0.5 L liquid cultures but not in the preceding 5 mL cultures. Neither the employment of an array of alternative recA1 E. coli plasmid hosts, nor the lowering of the culture incubation temperature prevented the instability. However, after the introduction of this instability-prone plasmid into the recA13E. coli strain Stbl3, the transformed bacteria grew without being overrun by plasmid-free cells, reduction in the plasmid DNA yield or structural changes in plasmid DNA. Thus, E. coli strain Stbl3 conferred structural and maintenance stability to the otherwise instability-prone lentivirus-based recombinant plasmid, suggesting that this strain can be used for the faithful maintenance of similar stability-compromised plasmids in large-scale bacterial cultivations. In contrast to Stbl2, which is derived wholly from the wild type isolate E. coli K12, E. coli Stbl3 is a hybrid strain of mixed E. coli K12 and E. coli B parentage. Therefore, we speculate that genetic determinants for the benevolent properties of E. coli Stbl3 for safe plasmid propagation originate from its E. coli B ancestor.


The wisdom in the story: Clarifying assumptions about radical uncertainty and reasonableness in narrative judgment.
Human lives are radically uncertain. Making sense of such uncertainties is the hallmark of wisdom. Sense-making requires narratives, putting them in the center stage of human everyday decision-making. Yet what if radical uncertainty is a narrative itself? Moreover, do laypeople always consider such narratives irrational? Here we pose these questions to enrich a theory of choice under uncertainty.


Fibrotic interstitial lung diseases and air pollution: a systematic literature review.
Air pollution is hypothesised to be a risk factor for interstitial lung diseases (ILD). This study systematically reviewed the literature regarding the impact of air pollution on idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (ILD). A computer-assisted literature search of electronic databases was performed to identify studies focused on the association between ILDs and air pollution. Other inclusion criteria required that the article had to be: 1) original; 2) a prospective or retrospective study; and 3) fully published in English. Both randomised clinical trials and observational studies were considered. Only seven studies met the inclusion criteria. All studies investigated the relationship between pollution and IPF, except one that dealt with the relationship between pollution and hypersensitivity pneumonitis. Outcome measures included exacerbation of IPF, mortality, disease severity, prevalence of hypersensitivity pneumonitis, progression and incidence of IPF. On the whole, air pollution levels were negatively associated with outcomes in patients with IPF and fibrotic ILD outcome. The heterogeneity in the measurement and reporting of the end-points limited the performance of a quantitative synthesis of data. This systematic review provides supporting evidence linking exposure to air pollution to poor outcomes in patients with IPF and fibrotic ILD.


Thresholds of action potentials evoked by synapses on the dendrites of pyramidal cells in the rat hippocampus in vitro.
1. In this study we have measured the thresholds of action potentials and some properties of e.p.s.p.s (excitatory post-synaptic potentials) produced by activation of distal and proximal dendritic synapses in CA1 pyramidal cells in rat hippocampal slices. 2. Simultaneous intracellular and extracellular electrophysiological recordings were made from pyramidal cells. The two recording electrodes were positioned very close together to provide an accurate measurement of the transmembrane potential by subtraction of the extracellular field from the intracellular potential. 3. Two pairs of stimulating electrodes were placed in the stratum radiatum of area CA1. The proximal and distal afferents were stimulated alternately within a 15 s cycle and at an intensity to produce action potentials in about 50% of the trials. 4. At this stimulus intensity there was a slight difference in the mean 10-90% rise times of the e.p.s.p.s produced by stimulation of proximal and distal afferents. The ratio of the distal: proximal rise time was 1.27. 5. In those trials where the action potential failed there was also a significant difference in the time-to-peak of the e.p.s.p.s evoked from proximal or distal sites. The times-to-peak of the e.p.s.p.s from proximal stimulation were between 1.5 and 3.8 ms, whilst the times-to-peak from distal stimulation were longer (2.1-7.2 ms). 6. In 16/18 cells included in this study the thresholds for action potentials evoked by distal stimulation were significantly lower than those following proximal activation. The mean threshold for distal activation was 12 mV compared with 16 mV for proximal activation. 7. The threshold of action potentials activated by depolarizing current pulses appeared to be close to that for action potentials evoked from proximal synapses. 8. Whilst the shape indices of the e.p.s.p.s were slightly different when comparing transmembrane with conventional intracellular recordings, the thresholds of the action potentials were not affected by this procedure. 9. Possible explanations for the low threshold for action potentials evoked from distal synapses are discussed, including an active dendritic membrane and differences in inhibition.


[Role of noradrenaline of the dorsal hippocampus in the mechanism of self-stimulation reaction in rats].
In has been established that intrahippocampal bilateral injection of NA did not influence common frequency of lateral hypothalamic self stimulation. After the destruction of hippocampal NA - terminals of 6-OHDA increased the frequency of self stimulation and rearing. It is suggested that NA hippocampus inhibit the recall trace of the memory of sensory reinforcement stimuli in the course of stimulation "reward".


[Chondroid syringoma in the parotid region. Report of a case].
This is a case of a right cervical lump in a 19 years old woman, diagnosed of chondroid Syringoma, by means of Fine Needle Aspiration Cytology, and surgically treated. The AA. analyze clinical, histological, diagnostic and therapeutic aspects of the theme and make a review of the present-day literature.


Anti-inflammatory and cytotoxic compounds from Solanum macaonense.
One new cerebroside, macaocerebroside A (1), and 15 known compounds (2-16) were isolated from Solanum macaonense for the first time. In an antineutrophilic inflammatory assay, four caffeic acid derivatives (2-5) were active against superoxide anion generation with IC50 values of 3.3-4.8 μM; especially, 3 inhibited elastase release with an IC50 value of 4.0 μM. Additionally, kaempferol (8) also showed inhibition against elastase release with an IC50 value of 4.0 μM. In a cytotoxic assay, rutin (14) had selective moderate cytotoxicity toward human lung (A549), bladder (NTUB1), and prostate (DU145) cancer cell lines with IC50 values of 34.6, 41.3, and 31.8 μM, respectively.


[Ultraviolet exposure in childhood and in adulthood: which life period modifies the risk of melanoma more substantially?].
The paper is devoted to the analysis of the relationship between the frequency of sunburns in childhood and adulthood, respectively, and the occurrence of malignant melanoma of the skin. The analysis is based on case-control data of 603 melanoma cases and 627 population controls from 11 participating centers in seven European countries. The results confirm the increase in melanoma risk for an increasing number of sunburns during childhood and adulthood in the same magnitude of risk elevation. The maximum OR for the highest exposure category of more than five sunburns was during the childhood 2.0 (95%-CI: 1.2-3.5) and during the adulthood 2.1 (95%-CI: 1.4-3.3), respectively. The analysis of the joint effects of sunburns during child- and adulthood on melanoma development corroborated these findings. In this joint analysis an OR of 2.1 (95%-CI: 1.3-3.5) quantifies the melanoma risk of those with three or more sunburns during child- and adulthood, respectively, compared to those without any sunburns during these periods. The study does therefore provide no supporting evidence for the presence of "critical period" during childhood in which a higher melanoma risk due to sunburns has been suggested by other studies.


Genome-wide microRNA profiling of human temporal lobe epilepsy identifies modulators of the immune response.
Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disorder characterized by recurrent seizures. The pathogenic mechanisms underlying mTLE may involve defects in the post-transcriptional regulation of gene expression. MicroRNAs (miRNAs) are non-coding RNAs that control the expression of genes at the post-transcriptional level. Here, we performed a genome-wide miRNA profiling study to examine whether miRNA-mediated mechanisms are affected in human mTLE. miRNA profiles of the hippocampus of autopsy control patients and two mTLE patient groups were compared. This revealed segregated miRNA signatures for the three different patient groups and 165 miRNAs with up- or down-regulated expression in mTLE. miRNA in situ hybridization detected cell type-specific changes in miRNA expression and an abnormal nuclear localization of select miRNAs in neurons and glial cells of mTLE patients. Of several cellular processes implicated in mTLE, the immune response was most prominently targeted by deregulated miRNAs. Enhanced expression of inflammatory mediators was paralleled by a reduction in miRNAs that were found to target the 3'-untranslated regions of these genes in reporter assays. miR-221 and miR-222 were shown to regulate endogenous ICAM1 expression and were selectively co-expressed with ICAM1 in astrocytes in mTLE patients. Our findings suggest that miRNA changes in mTLE affect the expression of immunomodulatory proteins thereby further facilitating the immune response. This mechanism may have broad implications given the central role of astrocytes and the immune system in human neurological disease. Overall, this work extends the current concepts of human mTLE pathogenesis to the level of miRNA-mediated gene regulation.


Conformational variation of surface class II MHC proteins during myeloid dendritic cell differentiation accompanies structural changes in lysosomal MIIC.
Dendritic cells (DC), uniquely among APC, express an open/empty conformation of MHC class II (MHC-II) proteins (correctly folded molecules lacking bound peptides). Generation and trafficking of empty HLA-DR during DC differentiation are investigated here. HLA-DR did not fold as an empty molecule in the endoplasmic reticulum/trans-Golgi network, did not derived from MHC/Ii complexes trafficking to the cell surface, but was generated after invariant chain degradation within lysosomal-like MHC-II rich compartments (MIIC). In pre-DC, generated from monocytes cultured in the presence of GM-CSF, Lamp-1(+)MHC-II(+) compartments are predominantly electron dense and, in these cells, empty MHC-II molecules accounts for as much as 20% of total surface HLA-DR. In immature DC, generated in presence of GM-CSF and IL-4, empty HLA-DR reside in multilamellar MIIC, but are scarcely observed at the cell surface. Thus, the morphology/composition of lysosomal MIIC at different DC maturational stages appear important for surface egression or intracellular retention of empty HLA-DR. Ag loading can be achieved for the fraction of empty HLA-DR present in the "peptide-receptive" form. Finally, in vivo, APC-expressing surface empty HLA-DR were found in T cell areas of secondary lymphoid organs.


Importance of catecholamine release for the functional action of intrastriatal implants of adrenal medullary cells: pharmacological analysis and in vivo electrochemistry.
The aim of the present experiments was to test whether adrenal chromaffin cells implanted into the striatum of rats could exert a functional effect through a release of catecholamines. A cell suspension obtained from bovine adrenal medulla was implanted unilaterally into the striatum. The striatal dopaminergic input was extensively destroyed beforehand to preclude the possibility of reinnervation of the striatum by endogenous dopaminergic neurons. The functional influence of the implant was tested through the measurement of drug-induced rotation, while catecholamine release was measured subsequently in the same animals by in vivo electrochemistry. Transplant survival, as shown by the immunohistochemical analysis performed at the end of the in vivo experiments, was highly variable. Surviving chromaffin cells maintained their endocrine morphology and no reinnervation of the host striatum could be detected. Rotation of the animals evoked by apomorphine (0.1 mg/kg, sc) or amphetamine (5.0 mg/kg, ip) following the lesion was left uninfluenced following transplantation, even when a large transplant was recovered. On the other hand, nicotine (0.5 mg/kg, sc) evoked a strong contraversive rotational response in the transplant-bearing animals. This response could not be ascribed to the central effect of substances released peripherally and entering the nervous system through the blood-brain barrier opened by the implantation procedure, as it could not be found in animals bearing implants of other peripheral endocrine tissue, viz, pituitary. The effect of nicotine was not blocked by the pretreatment of the animals with either the opiate antagonist naloxone (2.5 mg/kg, 10 min) or the dopamine receptor blocker pimozide (0.5 mg/kg, 1 h), although the latter pretreatment blocked the amphetamine-evoked rotation. No spontaneous catecholamine release could be detected from the implanted chromaffin cells by in vivo electrochemistry, while treatment with amphetamine or nicotine did evoke a release. The results suggest that the functional effects of such intrastriatal grafts of chromaffin cells, reported in previous studies, cannot be explained by the secretion from the grafted cells of catecholamines into the denervated striatum. On the other hand the results obtained following the pharmacological stimulation of these cells indicate that adrenal grafts can, under suitable conditions, influence the functioning of the host nervous system.


Microscopic malaria parasitemia diagnosis and grading on benchmark datasets.
Malaria parasitemia diagnosis and grading is hard and still far from perfection. Inaccurate diagnosis and grading has caused tremendous deaths rate particularly in young children worldwide. The current research deeply reviews automated malaria parasitemia diagnosis and grading in thin blood smear digital images through image analysis and computer vision based techniques. Actually, state-of-the-art reveals that current proposed practices present partially or morphology dependent solutions to the problem of computer vision based microscopy diagnosis of malaria parasitemia. Accordingly, a deep appraisal of the current practices is investigated, compared and analyzed on benchmark datasets. The open gaps are highlighted and the future directions are laid down for a complete automated microscopy diagnosis for malaria parasitemia based on those factors that have not been affected by other diseases. Moreover, a general computer vision framework to perform malaria parasitemia estimation/grading is constructed in universal directions. Finally, remaining problems are highlighted and possible directions are suggested. RESEARCH HIGHLIGHTS: The current research presents a microscopic malaria parasitemia diagnosis and grading of malaria in thin blood smear digital images through image analysis and computer vision based techniques. The open gaps are highlighted and future directions for a complete automated microscopy diagnosis of malaria parasitemia mentioned.


Incident dementia in kidney transplantation recipients: a matched comparative nationwide cohort study in South Korea.
Recent studies have shown that patients with end-stage renal disease (ESRD) are at elevated risk of dementia. However, whether kidney transplantation (KT) lowers the risk for incident dementia remains unclear. From the Korean National Health Insurance Service database, we identified incident KT recipients aged ≥40 years without any history of dementia between 2007 and 2015. We also established a pair of age-, sex-, and inclusion year-matched control cohorts of patients with incident dialysis-dependent ESRD and members of the general population (GP) without a history of dementia, respectively. Cases of incident all-cause dementia, including Alzheimer disease (AD), vascular dementia (VD), and other kinds of dementia, were obtained from baseline until December 31, 2017. We followed 8,841 KT recipients, dialysis-dependent ESRD patients, and GP individuals for 48,371, 28,649, and 49,149 patient- years, respectively. Their mean age was 52.5 years, and 60.6% were male. Over the observation period, 55/43/19 KT recipients, 230/188/75 dialysis-dependent ESRD patients, and 38/32/14 GP individuals developed all-cause dementia/AD/VD. The risks of incident all-cause dementia, AD, and VD in KT recipients were similar to those in GP (hazard ratio: 0.74 [p = 0.20], 0.74 [p = 0.24], and 0.59 [p = 0.18], respectively) and significantly lower than those in dialysis-dependent ESRD patients (hazard ratio: 0.17 [p < 0.001], 0.16 [p < 0.001], and 0.16 [p < 0.001], respectively). Older age and diabetes mellitus at the time of KT were risk factors for incident all-cause dementia and AD in KT recipients. This is the first study to show a beneficial impact of KT on incident dementia compared to dialysis dependency.


Onset of the COVID-19 pandemic reduced active time in patients with implanted cardiac devices.
Physical inactivity and sedentary behavior are modifiable risk factors for chronic disease and all-cause mortality that may have been negatively impacted by the COVID-19 shutdowns. Accelerometry data was retrospectively collected from 332 permanent pacemaker (PPM) and 244 implantable cardiac defibrillation (ICD) patients for 6 time points: March 15-May 15, 2020 (pandemic period), January 1-March 14, 2020, October 1-December 31, 2019, March 15-May 15, 2019, January 1-March 14, 2019, and October 1-December 31, 2018. Paired t-tests, with Bonferroni correction, were used to compare time periods. Activity significantly decreased during the pandemic period compared to one year prior by an average of 0.53 ± 1.18h/day (P < 0.001) for PPM patients and 0.51 ± 1.2h/day (P < 0.001) for ICD patients. Stratification of subjects by active time (< 2 versus ≥ 2h/day) showed patients with < 2h, particularly those with ICDs, had modestly greater activity reductions with the pandemic onset. Logistical regression analyses suggest a trend toward a greater reduction in active time at the onset of the pandemic and an increased risk of hospital or emergency department (ED) admission for PPM patients, but not ICD patients. The onset of the pandemic in the United States was associated with a significant drop in PPM and ICD patient active hours that was modestly more pronounced in less active patients and cannot be explained by one year of aging or seasonal variation. If sustained, these populations may experience excess cardiovascular morbidity.


Progesterone receptor isoform (A/B) ratio of human fetal membranes increases during term parturition.
The role of progesterone in the control of human parturition remains unsettled. Because there is no systemic progesterone withdrawal before the onset of labor, a 'functional progesterone withdrawal' has been proposed to be operative before human parturition. This may be accomplished by a change in the density of the progesterone receptor (PR) isoforms in myometrium and fetal membranes. The purpose of our study was to determine if spontaneous term labor is associated with changes of PR isoforms (PR-A and PR-B) in the fetal membranes. Fetal membranes were obtained from women undergoing elective cesarean delivery at term (not in labor group), and from women with a vaginal delivery (labor group). The expression of PR isoforms was assessed by Western blot analysis of amnion and chorio-decidua. Densitometric analysis of PR-A/PR-B ratio was performed. Immunohistochemistry with specific antibodies to PR-A and PR-B was done. Nonparametric statistics were used for analysis. 1) The predominant isoform of PR in women not in labor was PR-B, and PR-A in patients in labor. The ratio of PR-A/PR-B in fetal membranes was significantly higher in women in labor than in those not in labor (for amnion, median 4.3, range [0.9-8.4] vs median 0.4, range [0.3-2.6], P < .001; for chorio-decidua, median 2.0, range [1.1-19.2] vs median 1.2, range [0.1-2.0], P < .05). 2) Fetal membranes expressed both types of PR. 3) Immunohistochemistry showed the presence of PR-A and PR-B in the cytoplasm of amnion epithelial cells, chorion trophoblast, and decidual cells. Human parturition at term is associated with changes in PR isoforms in the fetal membranes and, thus, a local 'functional progesterone withdrawal' may operate in human parturition through this mechanism.


Enantioselective LC-MS/MS determination of antidepressants, β-blockers and metabolites in agricultural soil, compost and digested sewage sludge.
In this work, an analytical method was optimised and validated for the simultaneous extraction and enantioselective determination of chiral β-blockers, antidepressants and two of their metabolites in agricultural soils, compost and digested sludge. Sample treatment was based on ultrasound-assisted extraction and extract clean-up by dispersive solid-phase extraction. Analytical determination was carried out by liquid chromatography-tandem mass spectrometry using a chiral column. Enantiomeric resolutions were in the range from 0.71 to 1.36. Accuracy was in the range from 85 to 127% and precision, expressed as relative standard deviation, was lower than 17% for all the compounds. Method quantification limits were below 1.21-52.9 ng g-1 dry weight (dw) in soil, 0.76-35.8 ng g-1 dw in compost and 13.6-90.3 ng g-1 dw in digested sludge. Application to real samples revealed enantiomeric enrichment in the range especially in compost and digested sludge (enantiomeric fractions up to 1).


Drosophila wing-spot test: improved detectability of genotoxicity of polycyclic aromatic hydrocarbons.
The somatic mutation and recombination tests (SMART) using eyes or wings in the fruit fly Drosophila melanogaster are flexible and sensitive systems for the detection of genotoxicity of individual chemical compounds and complex mixtures. It is of special interest that adults and larvae possess cytochrome P-450-dependent activation systems able to metabolize most promutagens, e.g., nitrosamines, aflatoxins, pyrrolizidine alkaloids, safrole, etc. The polycyclic aromatic hydrocarbons (PAHs) represent a class of promutagens poorly detectable in Drosophila genotoxicity systems. Therefore, new tester strains for the wing-spot test were constructed by introducing chromosomes 1 and 2 from a wild-type strain with increased cytochrome P-450-dependent metabolism linked to a gene on chromosome 2. Previous investigations with the new strains showed their increased detection capability for diethylnitrosamine. Comparative tests with the 3 PAHs benzo[a]pyrene, benz[a]anthracene and 7,12-dimethylbenz[a]anthracene demonstrate, in a reproducible way, that with the new strains all 3 can be detected as active genotoxic compounds. The dose-response curves for all compounds show a plateau with higher exposures. This is interpreted as indicative of a saturation of the cytochrome P-450-dependent activation systems.


The translocation of transportin-cargo complexes through nuclear pores is independent of both Ran and energy.
Active transport between nucleus and cytoplasm proceeds through nuclear pore complexes (NPCs) and is mediated largely by shuttling transport receptors that use direct RanGTP binding to coordinate loading and unloading of cargo [1] [2] [3] [4]. Import receptors such as importin beta or transportin bind their substrates at low RanGTP levels in the cytoplasm and release them upon encountering RanGTP in the nucleus, where a high RanGTP concentration is predicted. This substrate release is, in the case of import by the importin alpha/beta heterodimer, coupled directly to importin beta release from the NPCs. If the importin beta -RanGTP interaction is prevented, import intermediates arrest at the nuclear side of the NPCs [5] [6]. This arrest makes it difficult to probe directly the Ran and energy requirements of the actual translocation from the cytoplasmic to the nuclear side of the NPC, which immediately precedes substrate release. Here, we have shown that in the case of transportin, dissociation of transportin-substrate complexes is uncoupled from transportin release from NPCs. This allowed us to dissect the requirements of translocation through the NPC, substrate release and transportin recycling. Surprisingly, translocation of transportin-substrate complexes into the nucleus requires neither Ran nor nucleoside triphosphates (NTPs). It is only nuclear RanGTP, not GTP hydrolysis, that is needed for dissociation of transportin-substrate complexes and for re-export of transportin to the cytoplasm. GTP hydrolysis is apparently required only to restore the import competence of the re-exported transportin and, thus, for multiple rounds of transportin-dependent import. In addition, we provide evidence that at least one type of substrate can also complete NPC passage mediated by importin beta independently of Ran and energy.


Ischemic stroke-related gene expression profiles across species: a meta-analysis.
Stroke patients are often left with permanent disabilities with no regenerative treatment options. Unbiased RNA sequencing studies decoding the transcriptional signature of stroked tissue hold promise to identify new potential targets and pathways directed to improve treatment for stroke patients. Here, gene expression profiles of stroked tissue across different time points, species, and stroke models were compared using NCBI GEO database. In total, 34 datasets from mice, rats, humans, and primates were included, exploring gene expression differences in healthy and stroked brain tissue. Distinct changes in gene expression and pathway enrichment revealed the heterogenicity of the stroke pathology in stroke-related pathways e.g., inflammatory responses, vascular repair, remodelling and cell proliferation and adhesion but also in diverse general, stroke-unrelated pathways that have to be carefully considered when evaluating new promising therapeutic targets.


Time of birth and the risk of neonatal death.
To assess whether mortality is increased in the United States in infants born at night, we compared case-mix adjusted neonatal mortality for low- and high-risk infants born during the daytime (7 am to 6 pm), early night (7 pm to 12 am), and late night (1 am to 6 am). California linked birth-death certificate data on 3,363,157 infants, weighing more than 500 g and born without lethal congenital anomalies in 1992-1999, were analyzed. Logistic regression, adjusting for birth weight, gender, prenatal care initiation, maternal hypertension, eclampsia, diabetes, and placental abruption/previa, was used to estimate the relationship between neonatal mortality and time of birth. The overall neonatal mortality was 2.08 deaths per 1,000 live births. Neonatal mortality was 1.88 for daytime births, increasing to 2.37 for early night and 2.31 for late night births. After adjusting for case mix, early night births had a 12% increase and late night births a 16% increase in the odds of neonatal death, an excess that accounts for 9.6% of all neonatal deaths. Mortality was increased for night births that were less than 1,500 g or more than 1,500 g, singletons or multiples, and those delivered vaginally or by cesarean. The increased risk was identified in hospitals that provide intermediate, community, and regional neonatal intensive care, but not in hospitals that provide primary care. Identifying the causal factors and reducing the increased burden of mortality for infants born at night should be a major priority for perinatal medicine.


Control of the bifunctional O2 -sensor kinase NreB of Staphylococcus carnosus by the nitrate sensor NreA: Switching from kinase to phosphatase state.
The NreB-NreC two-component system of Staphylococcus carnosus for O2 sensing cooperates with the accessory nitrate sensor NreA in the NreA-NreB-NreC system for coordinated sensing and regulation of nitrate respiration by O2 and nitrate. ApoNreA (NreA in the absence of nitrate) interacts with NreB and inhibits NreB autophosphorylation (and activation). NreB contains the phosphatase motif DxxxQ. The present study shows that NreB on its own was inactive for the dephosphorylation of the phosphorylated response regulator NreC (NreC-P), but co-incubation with NreB and NreA stimulated NreC-P dephosphorylation. Either the presence of NreA·NO3- instead of apoNreA or mutation of the phosphatase motif (D160 or Q164) of NreB abrogated phosphatase activity of NreB. Phosphatase activity was observed for anoxic (active) NreB as well as oxic NreB, therefore the functional state of NreB is not relevant for phosphatase activity. Thus, NreB is a bifunctional sensor kinase with an integral cryptic phosphatase activity. Activation of phosphatase activity and dephosphorylation of NreC-P requires NreA as a cofactor. Accordingly, NreA and nitrate have major and dual roles in NreA-NreB-NreC regulation by (i) inhibiting NreB phosphorylation and (ii) triggering a kinase/phosphatase switch of NreB when present as apoNreA.


Novel immunoassay for diagnosis of ongoing Clostridioides difficile infections using serum and medium enriched for newly synthesized antibodies (MENSA).
Clostridioides difficile infections (CDI) have been a challenging and increasingly serious concern in recent years. While early and accurate diagnosis is crucial, available assays have frustrating limitations. Develop a simple, blood-based immunoassay to accurately diagnose patients suffering from active CDI. Uninfected controls (N = 95) and CDI patients (N = 167) were recruited from Atlanta area hospitals. Blood samples were collected from patients within twelve days of a positive CDI test and processed to yield serum and PBMCs cultured to yield medium enriched for newly synthesized antibodies (MENSA). Multiplex immunoassays measured Ig responses to ten recombinant C. difficile antigens. Sixty-six percent of CDI patients produced measurable responses to C. difficile antigens in their serum or MENSA within twelve days of a positive CDI test. Fifty-two of the 167 CDI patients (31%) were detectable in both serum and MENSA, but 32/167 (19%) were detectable only in MENSA, and 27/167 (16%) were detectable only in serum. We describe the results of a multiplex immunoassay for the diagnosis of ongoing CDI in hospitalized patients. Our assay resolved patients into four categories: MENSA-positive only, serum-positive only, MENSA- and serum-positive, and MENSA- and serum-negative. The 30% of patients who were MENSA-positive only may be accounted for by nascent antibody secretion prior to seroconversion. Conversely, the serum-positive only subset may have been more advanced in their disease course. Immunocompromise and misdiagnosis may have contributed to the 34% of CDI patients who were not identified using MENSA or serum immunoassays. While there was considerable overlap between patients identified through MENSA and serum, each method detected a distinctive patient group. The combined use of both MENSA and serum to detect CDI patients resulted in the greatest identification of CDI patients. Together, longitudinal analysis of MENSA and serum will provide a more accurate evaluation of successful host humoral immune responses in CDI patients.


The effects of bovine serum albumin and a form of cationised ferritin upon the molecular selectivity of the walls of single frog capillaries.
Single frog mesenteric capillaries have been perfused with Ringer solutions containing the neutral macromolecule Ficoll 70 at a concentration of 40 mg ml-1, while the tissues have been washed with Ringer solution containing no macromolecules but otherwise of similar composition. The effective osmotic pressures (sigma delta II) set up across the capillary wall by the Ficoll 70 were used to assess the wall's molecular selectivity. The hydraulic conductivities, Lp, of the capillary walls were also measured. In seven capillaries the addition of bovine serum albumin (BSA) to the perfusate at concentrations of 1 and 10 mg ml-1 increased sigma delta II from a mean value of 7.14 +/- 1.81 cm H2O to one of 18.71 +/- 2.33 cm H2O and at the same time halved Lp. In another eight capillaries, the addition of a form of cationised ferritin (CF) to the perfusate at a concentration of 1 mg ml-1 increased sigma delta II from a mean value of 5.69 +/- 0.87 cm H2O to one of 16.69 +/- 0.262 cm H2O and reduced Lp to between a third and a half of its original value. In a further seven capillaries, the addition of native ferritin at a concentration of 1 mg ml-1 to the perfusate had no effect on either sigma delta II or Lp. It is suggested that both CF and BSA increase the reflection coefficients of capillary walls to Ficoll 70 by binding to the surface coat of the endothelium. The results are discussed in terms of a development of the fiber matrix theory of Curry and Michel (1980).


Quantitative real-time PCR detection of adenovirus in clinical blood specimens: a comparison of plasma, whole blood and peripheral blood mononuclear cells.
Detection and quantification of adenovirus (ADV) in peripheral blood specimens has become an increasingly important tool in the management of immunosuppressed patients. Investigators have described the use of whole blood (WB), peripheral blood mononuclear cells (PBMC), serum and plasma but no studies have compared the utility of these different sample types for use in a clinical diagnostic assay. To determine the optimal blood compartment for quantitative real-time measurement of adenovirus in peripheral blood specimens. WB, PBMC, and plasma representing 338 samples from 148 patients were tested for ADV by quantitative real-time PCR (qrt-PCR) and the results compared for concordance of both qualitative sensitivity and viral load among positive specimens. There was no significant difference in qualitative sensitivity among the three tested specimen types. Quantitative values of WB and plasma were similar and tended to be greater than those found in PBMC samples. Comparison of consecutive positive samples within individual patients showed that viral loads tracked similarly over time, irrespective of the sample type tested. While WB and plasma do not offer a significant increase in sensitivity over PBMC, they may offer benefits in terms of reduced processing costs and laboratory turn around time.


Mesh position for hernia prophylaxis after midline laparotomy: A systematic review and network meta-analysis of randomized clinical trials.
Mesh can be used to prevent incisional hernia (IH) occurrence. However, the effect of various mesh positions has never been compared. This study aimed to compare and rank the effect and safety of various mesh-augmented fascia closure techniques on hernia prophylaxis in midline laparotomy. MEDLINE and SCOPUS were searched from inception to December 2019. Randomized clinical trials (RCTs) were eligible if they met the following criteria: comparison of any of the following interventions: onlay (OM), retrorectus (RM), preperitoneal (PM), intraperitoneal mesh (IM) augmentation, and primary suture closure (PSC); and reporting on any of these outcomes: IH, wound infection, seroma, hematoma, and dehiscence. Two independent reviewers extracted data and assessed the risk of bias. A two-stage random-effect network meta-analysis was performed, then intervention effects were pooled and ranked accordingly. A total of 20 RCTs were eligible. Only OM and RM showed a significantly lower risk of IH than PSC with pooled risk ratios (RRs), 95% confidence intervals (95%CI) of 0.24 (0.12, 0.46) and 0.32 (0.16, 0.66), and number needed to treat (NNTs) of 4 and 5, respectively. However, OM showed a significantly higher risk of seroma than PSC (RR 2.21 (1.44, 3.39) with a number needed to harm (NNH) of 14). Most mesh placements showed a higher risk of wound infection, except for RM, but none of these was significantly different. All mesh techniques, except RM, showed a reduction in dehiscence, but again these were not significantly different. OM and RM provided the most effective IH prevention relative to PSC. However, OM had a higher rate of seroma than RM and PSC. Other complications, including wound infection, hematoma, and dehiscence, were not significantly observed among these fascia closure techniques.


P3/P3N-PIPO of PVY interacting with BI-1 inhibits the degradation of NIb by ATG6 to facilitate virus replication in N. benthamiana.
Autophagy not only plays an antiviral role but also can be utilized by viruses to facilitate virus infection. However, the underlying mechanism of potato virus Y (PVY) infection against plant autophagy remains unclear. BI-1, localizing to the endoplasmic reticulum (ER), is a multifunctional protein and may affect the virus infection. In this study, Y2H, BiFC, qRT-PCR, RNA-Seq, WB and so on were used for research. P3 and P3N-PIPO of PVY can interact with the Bax inhibitor 1 (BI-1) of N. benthamiana. However, BI-1 knockout mutant showed better growth and development ability. In addition, when the BI-1 gene was knocked out or knocked down in N. benthamiana, the PVY-infected mutant showed milder symptoms and lower virus accumulation. Analysis of transcriptome data showed that the deletion of NbBI-1 weakened the gene expression regulation induced by PVY infection and NbBI-1 may reduce the mRNA level of NbATG6 by regulated IRE1-dependent decay (RIDD) in PVY-infected N. benthamiana. The expression level of the ATG6 gene of PVY-infected WT was significantly down-regulated, relative to the PVY-infected mutant. Further results showed that ATG6 of N. benthamiana can degrade NIb, the RNA-dependent RNA polymerase (RdRp) of PVY. NbATG6 has a higher mRNA level in PVY-infected BI-1 knockout mutants than in PVY-infected WT. The interaction of P3 and/or P3N-PIPO of PVY with BI-1 decrease the expression of the ATG6 gene might be mediated by RIDD, which inhibits the degradation of viral NIb and enhances viral replication.


Dynamic needle tip positioning versus the angle-distance technique for ultrasound-guided radial artery cannulation in adults: a randomized controlled trial.
Ultrasound guidance can increase the success rate and reduce the incidence of complications of arterial cannulation. There are few studies on the utility of the dynamic needle tip positioning (DNTP) technique versus the angle-distance (AD) technique for ultrasound-guided radial arterial cannulation in adult surgical patients. We assessed and compared the success rates and incidences of complications of these two short-axis out-of-plane techniques. A total of 131 adult surgical patients were randomized into DNTP and AD groups to undergo ultrasound-guided radial artery cannulation. The primary outcome was first-pass success without posterior wall puncture. The secondary outcomes included the first-pass success rate, 10-min overall success rate, cannulation time, posterior wall puncture, and the number of skin punctures. The first-pass success rates without posterior wall puncture were 53.8% in the DNTP group and 44.6% in the AD group (RR = 1.22, 95% CI: 0.86-1.72; P = 0.26). The cannulation time was significantly longer (P = 0.01) in the DNTP group [79.65 (54.3-109.4) seconds] than in the AD group [47.6 (24.9-103.8) seconds]. The posterior wall puncture rate was significantly lower (P = 0.002) in the DNTP group (29.2%) than in the AD group (56.1%; RR = 0.56, 95% CI: 0.42-0.82). There were no significant differences in the first-pass success rate, with or without arterial posterior wall puncture, or in the 10-min overall success rate between the DNTP and AD groups. However, the cannulation time was longer and the posterior wall puncture rate was lower in the DNTP group. The trial was registered at www.clinicaltrials.gov (No: NCT03656978 ). Registered 4 September 2018.


Implementation of Choice from Participants' Perspectives: A Study of Community Mental Healthcare Reform in Sweden.
The aim of this study was to explore participants' experiences and opinions about a free-choice system in relation to policy objectives articulated by the national government and local authorities. A case study was conducted. Thirty-five informants participated. Qualitative interviews were undertaken. Results are discussed on how to address different dimensions of choice, not only where, but also what, by whom, how much, and when. They also concern how to design systems that in some ways ensure predictability and continuity to avoid unwanted harm caused by the unpredictability embedded in competitive choice systems. Finally, different aspects of quality need to be addressed.


Burn sera mediated effects on the E-rosetting property of normal active T1 cells.
This study investigates the suppressive effects of burn sera on normal active T1 cells. The results revealed that burn sera collected from survivors and non-survivors during the initial 'shock' phase caused varied effects on the 'E' rosetting properties of normal active T1 cells. However, unlike non-survivor sera convalescent or recovery sera failed to block the 'E' rosetting property of T1 cells. Furthermore, cold incubation in fetal calf sera (FCS) failed to abrogate the loss of T1 cells which were exposed to non-survivor (early) sera; these samples also revealed the presence of antigenic factors. Our experiments were extended to investigate the mechanisms resulting in the irreversible change, and showed that the inhibiting factors could be acting at the microtubular level of the cell cortex.


Quantification of interleukin-6 mRNA in wallerian degeneration by competitive reverse transcription polymerase chain reaction.
Following peripheral nerve injury, cytokines might be critically involved in regulating the cellular response within the lesioned nerve but are frequently difficult to measure due to their low abundancy. Competitive quantitative RT-PCR assays are potentially useful in quantifying cytokine mRNAs in small tissue samples but frequently do not fulfill the theoretical demands on proportional amplification of natural and standard sequences. Using this technique, we constructed standard curves for rat interleukin (IL)-6 mRNA with strictly proportional slopes and shifts when varying natural and standard RNA concentrations. A strong and transient increase in IL-6 mRNA was found in both nerve stumps 12 h after rat sciatic nerve transection, with low expression already in uninjured rat sciatic nerves. IL-6 might be involved in regulating the cellular response to peripheral nerve injury, and standard curves obtained by independent variation of standard and natural RNA are helpful in detecting and controlling experimental variables and pitfalls in competitive RT-PCR assays, thus increasing their reliability and reproducibility.


Shortened Tuberculosis Treatment for People with HIV in South Africa. A Model-based Evaluation and Cost-effectiveness Analysis.
Rationale: Recent tuberculosis treatment trials failed to show that some 4-month (4m) regimens were noninferior to conventional 6-month (6m) regimens for a composite clinical outcome. Novel shortened regimens may still have important clinical and economic benefits in populations with high loss to follow-up (LTFU) and in subgroups such as people with human immunodeficiency virus.Objectives: To identify scenarios in which a novel 4m regimen would be preferred to a conventional 6m regimen for treatment of drug-susceptible tuberculosis in people with human immunodeficiency virus in South Africa, in terms of short-term and long-term clinical and economic outcomes.Methods: We used the Cost-Effectiveness of Preventing AIDS Complications-International microsimulation model to project outcomes modeled on participants in the OFLOTUB trial. For calibration purposes, we did a base case analysis by applying trial-informed parameters for the 4m/6m regimens, including monthly LTFU during treatment (0.68%/0.83%), average monthly tuberculosis recurrence (0.65%/0.31%), and monthly drug costs (U.S. dollars [USD]25.90/3.70). We then evaluated different scenarios and 4m regimen characteristics, varying key parameters, including LTFU (informed by observational cohort data), recurrence, and cost. We projected outcomes, including 2-year mortality and life expectancy. We conducted a cost-effectiveness analysis, evaluating the incremental cost-effectiveness ratio of a 4m versus 6m regimen.Results: In the base case model analysis, risk of the composite unfavorable outcome in the 4m/6m groups was 19.8%/15.9%, similar to the trial; projected life expectancies were 22.1/22.3 years. In analyses of alternative scenarios and 4m regimen characteristics, a 4m regimen yielded lower risk of the composite unfavorable outcome than the conventional 6m regimen if LTFU increased to greater than 3.5%/mo or if average recurrence after a 4m regimen decreased to less than 0.45%/mo, and it yielded higher life expectancy if LTFU was greater than 3.5%/mo or if recurrence was less than 0.5%/mo. A 4m regimen was not cost-effective in the base case but became cost-effective (incremental cost-effectiveness ratio <USD940/yr of life saved) in two-way sensitivity analysis; for example, if LTFU was greater than or equal to 5.3%/mo and either average recurrence was less than or equal to 0.5%/mo or drug cost was less than or equal to USD15/mo.Conclusions: A novel shortened tuberculosis treatment regimen could improve outcomes such as survival despite conferring a higher recurrence risk, particularly in settings where LTFU is higher than that seen in recent trials.