Voxelwise meta-analysis of gray matter anomalies in Alzheimer's disease and mild cognitive impairment using anatomic likelihood estimation.
Many voxel-based morphometry studies in Alzheimer's disease (AD) and mild cognitive impairment (MCI) yielded not entirely consistent results. We conducted meta-analyses of gray matter anomalies to identify robust neuroanatomical changes between them. A systematic review of voxel-based morphometry studies of patients with AD and MCI relative to healthy comparison subjects in PubMed, Embase databases from January 1995 to 29 April, 2011 was conducted. The anatomical distribution of the coordinates of gray matter differences was meta-analyzed using anatomical likelihood estimation (ALE). Separate maps of gray matter changes were constructed, and subtraction meta-analysis between AD and MCI was also performed. Thirty-five AD studies and twenty-four MCI studies were included in the meta-analysis. Extensive gray matter deficits were present in the medial temporal lobe (including entorhinal cortex, hippocampus, parahippocampus, amygdala and uncus), thalamus, temporal, parietal, frontal and cingulate and insular cortices in AD. In MCI, gray matter reductions were identified in the medial temporal lobe (including entorhinal cortex, hippocampus, parahippocampus, amygdala and uncus), temporal, thalamus, and cingulate cortex. Subtraction meta-analysis found more severe gray matter deficit mainly in the left medial lobe (including parahippocampus, amygdala and hippocampus). Our meta-analysis identified similar distributions of neuroanatomical changes in AD and MCI, which are consistent with the hierarchical model of neuropathological alterations of neurofibrillary tangles in AD and MCI. Subtraction analysis provided evidence that the left MTL may be a neuroanatomical marker to evaluate disease progression from MCI to AD.


Cytotoxic Serrulatane-Type Diterpenoids from the Gorgonian Euplexaura sp. and Their Absolute Configurations by Vibrational Circular Dichroism.
Vibrational circular dichroism (VCD) method has become robust and reliable alternative for the stereochemical characterization of natural products. In this paper, three new serrulatane-type diterpenoids, euplexaurenes A-C (1-3), and a known metabolite, anthogorgiene P (4), were obtained from the South China Sea gorgonian Euplexaura sp. GXWZ-05. The absolute configuration of C-11 in 1-4, which was difficult to be determined by common means due to the high conformational flexibility of the eight-carbon aliphatic chain attached at C-4, was determined by VCD method, suggesting a new horizon to define the absolute configurations of natural products possessing chains. Compounds 1-4 were found to show selective cytotoxic activities against human laryngeal carcinoma (Hep-2) cell line with the IC50 values of 1.95, 7.80, 13.6 and 5.85 μM, respectively.


Vaccination of cats against emerging and reemerging zoonotic pathogens.
Many of the emerging infectious agents that threaten the human population are either directly zoonotic or involve animals, rather than humans, as their primary reservoir in nature. Vaccination of animals may be an important consideration for control of some of these diseases, and this review has specifically focused on the concept of vaccinating cats in the prevention of infection with T. gondii, B. henselae, and H. pylori. If we return to the considerations that were presented in Table III, T. gondii is really the only one of these three agents for which each of these "criteria" for vaccination is fulfilled at the present time. However, cats clearly play an important role in the epidemiology of infection with B. henselae and this is an organism for which we probably will and should see a vaccine for widespread and routine use in cats.


The role of bismuth nanoparticles in the inhibition of bacterial infection.
Bismuth (Bi) combinations have been utilized for the treatment of bacterial infections. In addition, these metal compounds are most frequently utilized for treating gastrointestinal diseases. Usually, Bi is found as bismuthinite (Bi sulfide), bismite (Bi oxide), and bismuthite (Bi carbonate). Newly, Bi nanoparticles (BiNP) were produced for CT imaging or photothermal treatment and nanocarriers for medicine transfer. Further benefits, such as increased biocompatibility and specific surface area, are also seen in regular-size BiNPs. Low toxicity and ecologically favorable attributes have generated interest in BiNPs for biomedical approaches. Moreover, BiNPs offer an option for treating multidrug-resistant (MDR) bacteria because they communicate directly with the bacterial cell wall, induce adaptive and inherent immune reactions, generate reactive oxygen compounds, limit biofilm production, and stimulate intracellular impacts. In addition, BiNPs in amalgamation with X-ray therapy as well as have the capability to treat MDR bacteria. BiNPs as photothermal agents can realize the actual antibacterial through continuous efforts of investigators in the near future. In this article, we summarized the properties of BiNPs, and different preparation methods, also reviewed the latest advances in the BiNPs' performance and their therapeutic effects on various bacterial infections, such as Helicobacter pylori, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli.


Comparison of cost changes due to the COVID-19 pandemic for Dermatology residency applications in the USA.
We performed a cost estimation of dermatology residency applications prior to COVID-19 pandemic restrictions (2016-2020) and during the COVID-19 pandemic (2021) and surveyed dermatology programme directors to assess the impact of virtual interviews. We found that COVID-19 virtual interviews significantly reduced the cost of applications. We understand that the changes forced by the pandemic were challenging and not ideal; however, the online aspect of interviews provided a way for applicants to save a significant amount of money.


Simultaneous determination of elbasvir and grazoprevir in their pharmaceutical formulation by synchronous fluorescence spectroscopy coupled to dual wavelength method.
In the present study, a sensitive, selective and accurate synchronous fluorescence spectroscopic method was utilized for simultaneous estimation of elbasvir and grazoprevir in their pharmaceutical formulation. The developed method based on measurement of the synchronous fluorescence intensity of the studied drugs at constant wavelength difference (Δλ) = 50 nm. Elbasvir can be determined directly at 312 nm without interference from grazoprevir. Grazoprevir can be determined by application of dual wavelength method by taking the difference in synchronous fluorescence intensity at 390 & 372 nm to remove interference from elbasvir. Calibration graphs were found to be linear over the concentration range of 50-700 ng/mL for elbasvir and 100-900 ng/mL for grazoprevir. The developed method was successfully applied to the quantitative analysis of the two drugs in Zepatier® tablets.


When confidence in a choice is independent of which choice is made.
For forced-choice two-alternative general-information questions, confidence in the correctness of the answer differed reliably for different questions, regardless of which answer was chosen. Results suggested that this choice-independent confidence is mediated by the domain familiarity of the question and by its tendency to bring to mind either few or many thoughts and considerations. Ratings of the questions on familiarity and accessibility yielded strong correlations with participants' confidence in whichever of two answers they had chosen, and with estimates of the percentage of participants who were likely to have chosen either of the answers in a previous experiment. The results were interpreted in terms of confirmation bias: Because items differ in the extent to which they bring to mind few or many pertinent thoughts, selective focusing on supportive evidence should yield a positive correlation between mean confidence in one answer and mean confidence in the alternative answer, as if there is no competition between them.


Stability of JC virus coding sequences in a case of progressive multifocal leukoencephalopathy in which the viral control region was rearranged markedly.
It is generally accepted that JC virus variants in the brains of patients with progressive multifocal leukoencephalopathy are generated from archetypal strains through sequence rearrangement (deletion and duplication, or deletion alone) in the control region. This change is thought to occur during persistence of JC virus in patients. The present study was performed to ascertain whether amino acid substitution in the viral proteins is involved in the generation and propagation of JCV variants with rearranged control regions. Many complete JC DNA clones were established from brain tissues (cerebellum, occipital lobe, and brainstem) autopsied in a case of progressive multifocal leukoencephalopathy in which multiple distinct control sequences were detected. Control and coding sequences were determined and compared among the JC DNA clones. Twenty-eight control-region and 20 coding sequences of JC virus were compared. Five rearranged control sequences were detected, but they could be classified into 3 groups that shared common structural features. Viral coding sequences were identical among clones with different control regions and among clones derived from different brain regions. In the present case, nucleotide substitution in the viral coding regions (and resultant amino acid change in the viral proteins) was involved neither in the genesis of rearranged JC virus variants nor in the proliferation of demyelinated lesions in the brain.


Kinetics of antibody response to Coxiella burnetii infection (Q fever): Estimation of the seroresponse onset from antibody levels.
From 2007 to 2009, the Netherlands experienced a major Q fever epidemic. Long-term serological follow-up of acute Q fever patients enabled the investigation of longitudinal antibody responses and estimating the onset of the seroresponse in individual patients. All available IgG and IgM phase I and II antibody measurements determined by immunofluorescence assay at month 3, 6, 12, and 48 from 2321 acute Q fever patients were retrospectively analyzed. Characteristic features of the antibody response were calculated. To model the seroresponse onset, serological data from patients diagnosed with a positive C. burnetii PCR test (n=364), and therefore with a known time of infection, were used as reference. In 9083 IgG samples and 3260 IgM samples large heterogeneity in shape and magnitude of antibody responses was observed. Phase II reached higher levels than phase I, and IgG antibodies were more persistent than IgM. The estimated seroresponse latency allowed for determining the time since start of the seroresponse from the concentrations of the different antibodies against C. burnetii. The extraordinary large serological dataset provides new insight into the kinetics of the immunoglobulins against C. burnetii antigens. This knowledge is useful for seroprevalence studies and helps to better understand infection dynamics.


DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice.
The oncofetal alpha-fetoprotein (AFP) is reexpressed in the majority of hepatocellular carcinomas and may be used as a target molecule for an immunotherapy or prophylaxis against this tumor. We investigated the potential of DNA vaccination with AFP-expressing plasmid DNA to induce an immune response against AFP-expressing tumor cells in DBA/2 mice. 62.5% of mice vaccinated with AFP-expressing plasmid DNA, rejected subcutaneous syngeneic AFP-expressing P815 tumors, whereas only 16.7% of mice vaccinated with control plasmid rejected these tumor cells (P=.03). Mean survival of mice after challenge with subcutaneous AFP-expressing tumor cells was prolonged for 8 days in mice vaccinated with AFP-expressing DNA (35 days) compared to mice vaccinated with control plasmid (27 days). To rule out possible autoimmune reactions against regenerating liver, which also reexpresses AFP, we evaluated the influence of AFP-specific DNA vaccination on liver regeneration in DBA/2 mice. Histologic quantification of proliferating hepatocytes and of the amount of necrotic liver tissue in carbon tetrachloride-damaged liver did not reveal statistically significant differences in mice vaccinated with AFP-expressing plasmid compared to control mice. These data suggest that AFP-specific DNA vaccination represents a useful tool to inhibit growth of AFP-expressing tumors in mice that does not affect liver regeneration.


Calmodulin activation and inhibition of skeletal muscle Ca2+ release channel (ryanodine receptor).
The calmodulin-binding properties of the rabbit skeletal muscle Ca2+ release channel (ryanodine receptor) and the channel's regulation by calmodulin were determined at < or = 0.1 microM and micromolar to millimolar Ca2+ concentrations. [125I]Calmodulin and [3H]ryanodine binding to sarcoplasmic reticulum (SR) vesicles and purified Ca2+ release channel preparations indicated that the large (2200 kDa) Ca2+ release channel complex binds with high affinity (KD = 5-25 nM) 16 calmodulins at < or = 0.1 microM Ca2+ and 4 calmodulins at 100 microM Ca2+. Calmodulin-binding affinity to the channel showed a broad maximum at pH 6.8 and was highest at 0.15 M KCl at both < or = 0.1 MicroM and 100 microM Ca2+. Under condition closely related to those during muscle contraction and relaxation, the half-times of calmodulin dissociation and binding were 50 +/- 20 s and 30 +/- 10 min, respectively. SR vesicle-45Ca2+ flux, single-channel, and [3H]ryanodine bind measurements showed that, at < or = 0.2 microM Ca2+, calmodulin activated the Ca2+ release channel severalfold. Ar micromolar to millimolar Ca2+ concentrations, calmodulin inhibited the Ca(2+)-activated channel severalfold. Hill coefficients of approximately 1.3 suggested no or only weak cooperative activation and inhibition of Ca2+ release channel activity by calmodulin. These results suggest a role for calmodulin in modulating SR Ca2+ release in skeletal muscle at both resting and elevated Ca2+ concentrations.


Effect of in-plane Mott-Schottky on the hydroxyl deprotonation in MoS2@Co3S4/NC heterostructure for efficient overall water splitting.
The development of clean energy sources such as hydrogen is indispensable for achieving the long-term goal of carbon neutrality by the mid-century. The utilization of renewable energy for power generation to electrolyze water for hydrogen production is one of the most desirable green hydrogen production methods. The cathode side of the decomposing water undergoes the oxygen precipitation reaction, and the oxygen precipitation mechanism can be divided into the adsorbed evolution mechanism (AEM) and lattice oxygen oxidation mechanism (LOM). Based on the adsorbed evolution mechanism (AEM), the deprotonation (DeP) process involving multiple electron transfers is central to determining the oxygen release. DeP is essentially a proton-transfer process that allows for the establishment of a bifunctional catalyst system with both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Consequently, an all-transition-metal-based MoS2@Co3S4/NC heterostructure was designed and constructed in this study for the efficient total decomposition of water. The MoS2@Co3S4/NC catalyst achieved the HER and OER current densities of 10 mA cm-2 at the low overpotential (56 mV, 243 mV) and showed excellent long-term durability among all samples. The Mott-Schottky effect is considered the driving force for the HER and DeP in the OER. This study proposes a rational design for bifunctionalized non-precious metal electrolytic water catalysts using the Mott-Schottky effect as a criterion.


VIP measurement in distinguishing Verner-Morrison syndrome and pseudo Verner-Morrison syndrome.
1. Plasma VIP immunoreactivity is always diagnostically raised in patients with pancreatic tumour causing the Verner-Morrison syndrome. 2. Human tumour VIP is physico-chemically similar to porcine VIP. 3. The only other situation in which plasma VIP is very elevated is in patients with ganglioneuroblastomas associated with diarrhoea. 4. VIP is not elevated in patients with diarrhoea associated with pancreatic islet hyperplasia, designated the pseudo Verner-Morrison syndrome.


Characterization of a p30 fraction from Rauscher leukemia virus which has an associated ATPase activity.
The p30 antigen from Rauscher leukemia virus (R-MuLV) was separated into two fractions by chromatography on either phosphocellulose or DEAE-cellulose. The p30-I and p30-II were indistinguishable immunologically or by isoelectrofocusing and gel electrophoresis. An ATPase activity was tightly associated with p30-II that could not be separated by ion-exchange chromatography, isoelectrofocusing, or glycerol velocity gradient sedimentation. The ATPase hydrolyzed the gamma phosphate from only ATP or dATP. Immunoglobulin directed against R-MuLV p30 completely inhibited the p30-II associated ATPase. Glycerol velocity gradient analysis showed that p30-I sedimented as a 30-kDa species while the p30-II and its associated ATPase sedimented as a 60-kDa species. The p30-II was converted entirely to a 30-kDa form by treatment with 0.2% (w/v) lithium dodecyl sulfate, suggesting that it represented a complexed species of p30. Finally, p30-II was found to stimulate the activity of R-MuLV reverse transcriptase, but p30-I had no effect on the activity of the enzyme. These results suggested the existence of at least two different forms of p30 in R-MuLV.


Complexity of modular neuromuscular control increases and variability decreases during human locomotor development.
When does modular control of locomotion emerge during human development? One view is that modularity is not innate, being learnt over several months of experience. Alternatively, the basic motor modules are present at birth, but are subsequently reconfigured due to changing brain-body-environment interactions. One problem in identifying modular structures in stepping infants is the presence of noise. Here, using both simulated and experimental muscle activity data from stepping neonates, infants, preschoolers, and adults, we dissect the influence of noise, and identify modular structures in all individuals, including neonates. Complexity of modularity increases from the neonatal stage to adulthood at multiple levels of the motor infrastructure, from the intrinsic rhythmicity measured at the level of individual muscles activities, to the level of muscle synergies and of bilateral intermuscular network connectivity. Low complexity and high variability of neuromuscular signals attest neonatal immaturity, but they also involve potential benefits for learning locomotor tasks.


Atrial fibrillation after but not before primary angioplasty for ST-segment elevation myocardial infarction of prognostic importance.
In patients with ST-segment elevation myocardial infarction (STEMI), it is uncertain whether atrial fibrillation has prognostic implications. There may be a difference between atrial fibrillation before and after reperfusion therapy. In patients with STEMI treated with primary percutaneous coronary intervention (PCI), ECGs were analysed before and after primary PCI. Of the 1623 patients with electrocardiographic data before primary PCI, 53 patients (3.3%) had atrial fibrillation. Patients with atrial fibrillation were older, were more often female, and less often had anterior MI location. Of the 1728 patients with electrocardiographic data after primary PCI, 52 patients (3.0%) had atrial fibrillation. Atrial fibrillation was more common in older patients and in those with Killip class >1. Also patients with occlusion of the right coronary artery or TIMI flow 0 before primary PCI more commonly had AF after the procedure. Not successful reperfusion was also associated with a higher incidence of AF after primary PCI. Although both atrial fibrillation before and after primary PCI were associated with increased mortality, multivariable analyses, adjusting for differences in age, gender and Killip class on admission, revealed that atrial fibrillation after PCI (OR 3.69, 95% CI 1.87-7.29) but not before PCI (OR 1.86, 95% CI 0.89-3.90) was independent and statistically significantly associated with long-term mortality. In patients with STEMI, atrial fibrillation after but not before primary PCI has independent prognostic implications. Possibly, atrial fibrillation after the PCI is a symptom of failed reperfusion and a sign of heart failure.


Evidence for a direct action of exogenous insulin on the pancreatic islets of diabetic mice: islet response to insulin pre-incubation.
Pancreatic islets were isolated by collagenase digest from normal (+/+) and severely diabetic (db/db) mice of the C57BL/Ks strain. Batches of islets from the diabetic mice were incubated for 1 h at 37 degrees C in Krebs-Ringer medium containing glucose (3 mmol/l), with or without mouse insulin (50 mU/l), before perifusion. When compared with untreated islets from the same digest, pre-incubation of islets from diabetic mice with insulin elicited a restoration of the biphasic insulin response to a glucose challenge which was indistinguishable from the response of the untreated, control islets from non-diabetic mice. Untreated diabetic islets showed no insulin response to glucose challenge, insulin values being very significantly lower than those of either non-diabetic or treated diabetic mouse islets (p = less than 0.005). The restoration of secretion in treated islets of diabetic mice was shown not to be an artefact. These observations provide evidence for a direct, as yet undefined, action of insulin on the beta cell of the diabetic mouse.


Carnosol attenuates bleomycin-induced lung damage via suppressing fibrosis, oxidative stress and inflammation in rats.
Bleomycin, an important toxic anti-cancer agent, induces pulmonary fibrosis. The significance of oxidative stress and inflammation in promoting of bleomycin-induced idiopathic pulmonary fibrosis (IPF) has been reported. Thus, we evaluated the protective effects of carnosol as a robust natural antioxidant and anti-inflammatory agent for bleomycin-related IPF in rats. Male Wistar rats (n = 40) were randomly assigned to five groups. Group 1 was administrated with saline (intratracheally) on day 7 and oral gavage of dimethyl sulfoxide (DMSO, 0.05%) from day 1 to day 28. Group 2 received a single dose of bleomycin (intratracheally, 7.5 UI/kg) on day 7 and oral gavage of saline for 28 days. Groups 3, 4 and 5 were administrated with bleomycin (single dose) on day 7, along with oral administration of carnosol (at doses 10, 20 and 40 mg/kg, respectively) from day 1 to day 28. The lungs were isolated to measure the histopathological and biochemical and inflammatory markers. Carnosol treatment significantly reduced malondialdehyde, nitric oxide, protein carbonyl, tumor necrosis factor- α, interleukin-6 levels and myeloperoxidase activity in the lungs of rats exposed to bleomycin. Also, lung glutathione content, catalase, glutathione peroxidase and superoxide dismutase activities significantly increased in the carnosol/bleomycin-treated group than the bleomycin group. Lung index, hydroxyproline content, fibrosis and histopathological changes, also significantly decreased by carnosol therapy. Treatment with carnosol can modulate biochemical and histological alterations caused by bleomycin. Thus, it can be regarded as an appropriate therapeutic approach for IPF.


Helios(®) Gene Gun-Mediated Transfection of the Inner Ear Sensory Epithelium: Recent Updates.
The transfection of vertebrate inner ear hair cells has proven to be challenging. Therefore, many laboratories attempt to use and improve different transfection methods. Each method has its own advantages and disadvantages. A particular researcher's skills in addition to available equipment and the type of experiment (in vivo or in vitro) likely determine the transfection method of choice. Biolistic delivery of exogenous DNA, mRNA, or siRNA, also known as Helios(®) Gene Gun-mediated transfection, uses the mechanical energy of compressed helium gas to bombard tissue with micron- or submicron-sized DNA or RNA-coated gold particles, which can penetrate and transfect cells in vitro or in vivo. Helios(®) Gene Gun-mediated transfection has several advantages: (1) it is simple enough to learn in a short time; (2) it is designed to overcome cell barriers even as tough as plant cell membrane or stratum corneum in the epidermis; (3) it can transfect cells deep inside a tissue such as specific neurons within a brain slice; (4) it can accommodate mRNA, siRNA, or DNA practically of any size to be delivered; and (5) it works well with various cell types including non-dividing, terminally differentiated cells that are difficult to transfect, such as neurons or mammalian inner ear sensory hair cells. The latter advantage is particularly important for inner ear research. The disadvantages of this method are: (1) low efficiency of transfection due to many variables that have to be adjusted and (2) potential mechanical damage of the tissue if the biolistic shot parameters are not optimal. This chapter provides a step-by-step protocol and critical evaluation of the Bio-Rad Helios(®) Gene Gun transfection method used to deliver green fluorescent protein (GFP)-tagged full-length cDNAs of myosin 15a, whirlin, β-actin, and Clic5 into rodent hair cells of the postnatal inner ear sensory epithelia in culture.


Stress amelioration potential of vitamin C in ruminants: a review.
Ruminants, as well as other livestock, can synthesize vitamin C (VC) in their liver, and therefore, dietary requirements from exogenous supplementation are often ignored. However, metabolic demand may be exceeded, leading to a decreased endogenous synthetic capacity of VC following exposure to stressful conditions. Such conditions include high thermal load, limited water intake (induced by water scarcity), physiological status and infectious diseases. The obvious consequences are decreased performance, susceptibility to infections and increased mortality. This review discusses the potential role of vitamin C in ruminants' stress management and summarizes the in vitro and in vivo research to date. The different administration routes, comparative advantages and supplementation outcomes on growth, production parameters and physiological status were also identified. Also, areas where there was a lack of evidence or controversy, including critical literature research gaps, were identified, while the mechanism of VC's actions on significant outcomes was explained.


Conventional, ultrasound-assisted, and accelerated-solvent extractions of anthocyanins from purple sweet potatoes.
Purple sweet potatoes (PSPs) are rich in anthocyanins. In this study, we investigated the extraction efficiency of anthocyanins from PSPs using conventional extraction (CE), ultrasound-assisted extraction (UAE), and accelerated-solvent extraction (ASE). Additionally, the effects of these extraction methods on antioxidant activity and anthocyanin composition of PSP extracts were evaluated. In order of decreasing extraction efficiency, the extraction methods were ASE>UAE>CE for anthocyanins (218-244 mg/100 g DW) and CE>UAE>ASE for total phenolics (631-955 mg/100 g DW) and flavonoids (28-40 mg/100 g DW). Antioxidant activities of PSP extracts were CE≈UAE>ASE for ORAC (766-1091 mg TE/100 g DW) and ASE>CE≈UAE for FRAP (1299-1705 mg TE/100 g DW). Twelve anthocyanins were identified. ASE extracts contained more diacyl anthocyanins and less nonacyl and monoacyl anthocyanins than CE and ASE extracts (P<0.05).


Epidural analgesia and the metabolic response to surgery.
The effect of epidural blockade on the metabolic and hormonal responses to pelvic surgery was investigated in 14 female patients. Central venous blood samples were collected every 30 minutes and analysed for free fatty acids, glycerol, beta-hydroxybutyrate, acetoacetate, glucose, lactate, pyruvate, cortisol and growth hormone concentrations. There was no change in fat and glucose metabolism except for a transient decrease in lipolysis after 30 minutes of surgery. Cortisol and growth hormone values were significantly increased (p less than 0.01) after 60 minutes. A small but statistically significant increase in blood lactate concentration was observed (p less than 0.01) and the concept of a "metabolic V/Q" abnormality is postulated to explain the lacticacidaemia.


Comparative activity of ciprofloxacin, ofloxacin, sparfloxacin, temafloxacin, CI-960, CI-990, and WIN 57273 against anaerobic bacteria.
The in vitro activities of seven fluoroquinolones against 290 anaerobes were determined by agar dilution. CI-960 and WIN 57273 inhibited greater than 95% of the strains at less than or equal to 2 micrograms/ml. CI-990 required less than or equal to 16 micrograms/ml. Clustering around 2 to 4 micrograms/ml was noted for Bacteroides fragilis group organisms with CI-990, sparfloxacin, and temafloxacin. Temafloxacin and sparfloxacin inhibited most strains at less than or equal to 2 micrograms/ml. B. fragilis was more susceptible to all quinolones than were the other B. fragilis group strains.


Gaussian process modeling in conjunction with individual patient simulation modeling: a case study describing the calculation of cost-effectiveness ratios for the treatment of established osteoporosis.
Individual patient-level models can simulate more complex disease processes than cohort-based approaches. However, large numbers of patients need to be simulated to reduce 1st-order uncertainty, increasing the computational time required and often resulting in the inability to perform extensive sensitivity analyses. A solution, employing Gaussian process techniques, is presented using a case study, evaluating the cost-effectiveness of a sample of treatments for established osteoporosis. The Gaussian process model accurately formulated a statistical relationship between the inputs to the individual patient model and its outputs. This model reduced the time required for future runs from 150 min to virtually-instantaneous, allowing probabilistic sensitivity analyses-to be undertaken. This reduction in computational time was achieved with minimal loss in accuracy. The authors believe that this case study demonstrates the value of this technique in handling 1st- and 2nd-order uncertainty in the context of health economic modeling, particularly when more widely used techniques are computationally expensive or are unable to accurately model patient histories.


Anti-TNF-α Therapy for Refractory Uveitis Associated with Behçet's Syndrome and Sarcoidosis: A Single Center Study of 131 Patients.
The efficacy of infliximab (IFX) and adalimumab (ADA) for treating Behçet's syndrome (BS) and sarcoidosis has not been compared adequately. We reviewed the medical records of patients with uveitis diagnosed at Tokyo Medical University Hospital and compared the efficacy of IFX and ADA for BS and the efficacy of ADA for sarcoidosis and BS. 68 patients in IFX group and 63 patients in ADA group were analyzed. In BS patients, IFX and ADA were both effective in improving uveitic macular edema (UME). ADA improved UME in BS but not in sarcoidosis patients. The efficacy of ADA in reducing doses of corticosteroids and glaucoma medications was better in sarcoidosis than in the BS group. Both IFX and ADA are efficacious in improving UME in BS patients. The reason that ADA improves UME better in BS than in sarcoidosis may be due to the difference in pathogenesis between these diseases.


Long-term results of in situ split-liver transplantation.
Split-liver transplantation (SLT) offers immediate expansion of the cadaver donor pool. The principal beneficiaries have been adult and pediatric recipients with excellent outcomes. This study analyzed a single-center experience of adult to adult in situ SLT in adult recipients. Fourteen consecutive adult-to-adult in situ SLT have been performed at our institution since 1998. The extended right lobe comprising segment 1 was transplanted in to adult patients, the left lateral segment, for pediatric transplants. Donors of SLT were significantly younger (P = .03) than those of whole liver transplants. Survival rates of patients receiving a split liver were 83%, 73%, and 73% at 1, 3, and 5 years after the transplant respectively and grafts of 73%, 73%, and 73% for SLT and 76%, 70%, and 66% for whole liver transplants (P = .44). The rate of biliary complication after SLT was 21%, which was comparable to that after whole organ transplantation (17%). The incidence of hepatic artery thrombosis and primary nonfunction was not significantly different between split liver and whole organ transplantation performed during the same time period (7% versus 4.6% P = .67 and 7% versus 2.6% P = .32, respectively). This limited single-center experience confirmed that both early and long-term results of SLT are comparable to those of traditional whole liver organ transplantation.


Exploring causal associations of alcohol with cardiovascular and metabolic risk factors in a Chinese population using Mendelian randomization analysis.
Observational studies suggest that moderate alcohol consumption may be protective for cardiovascular disease, but results may be biased by confounding and reverse causality. Mendelian randomization, which uses genetic variants as proxies for exposures, can minimise these biases and therefore strengthen causal inference. Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, we performed a Mendelian randomization analysis in 1,712 diabetes cases and 2,076 controls from Nantong, China. Analyses were performed using linear and logistic regression, stratified by sex and diabetes status. The A allele of rs671 was strongly associated with reduced odds of being an alcohol drinker in all groups, but prevalence of alcohol consumption amongst females was very low. The A allele was associated with reduced systolic and diastolic blood pressure and decreased total and HDL cholesterol in males. The A allele was also associated with decreased triglyceride levels, but only robustly in diabetic males. There was no strong evidence for associations between rs671 and any outcomes in females. Our results suggest that associations of alcohol consumption with blood pressure and HDL-cholesterol are causal. Alcohol also appeared to have adverse effects on triglyceride levels, although this may be restricted to diabetics.


Competitive accumulation of betaines by Escherichia coli K-12 and derivative strains lacking betaine porters.
Escherichia coli was grown in hyperosmotic media containing both glycine betaine and one other betaine. E. coli K-12 derivative WG439 (putP- proP- proU-) did not accumulate any of 15 betaines. Strains WG445 (putP- proP- proU+), WG443 (putP- proP+ proU-) and the control strains all accumulated less betaine, (CH3)3N(+)-(CH2)n-COO-, when n was greater than 1. Accumulation was not detectable when n = 5. Both L- and D-isomers of alpha-substituted betaines were accumulated by both strains WG443 and WG445, the D-isomers more slowly. Hydroxylated alpha-substituted betaines were accumulated relatively more through the osmoregulated transport protein ProU than through ProP. In actively growing cultures glycine betaine appeared to be the preferred substrate for accumulation, but the proportion of the second accumulated betaine increased as cultures approached stationary phase.


Temperature modulates the response of the thermophilous sea urchin Arbacia lixula early life stages to CO2-driven acidification.
The increasing abundances of the thermophilous black sea urchin Arbacia lixula in the Mediterranean Sea are attributed to the Western Mediterranean warming. However, few data are available on the potential impact of this warming on A. lixula in combination with other global stressors such as ocean acidification. The aim of this study is to investigate the interactive effects of increased temperature and of decreased pH on fertilization and early development of A. lixula. This was tested using a fully crossed design with four temperatures (20, 24, 26 and 27 °C) and two pH levels (pHNBS 8.2 and 7.9). Temperature and pH had no significant effect on fertilization and larval survival (2d) for temperature <27 °C. At 27 °C, the fertilization success was very low (<1%) and all larvae died within 2d. Both temperature and pH had effects on the developmental dynamics. Temperature appeared to modulate the impact of decreasing pH on the % of larvae reaching the pluteus stage leading to a positive effect (faster growth compared to pH 8.2) of low pH at 20 °C, a neutral effect at 24 °C and a negative effect (slower growth) at 26 °C. These results highlight the importance of considering a range of temperatures covering today and the future environmental variability in any experiment aiming at studying the impact of ocean acidification.


Oestrogen and progesterone receptor distribution in the cancerous breast.
To test the hypothesis that steroid hormone receptor expression is particularly pronounced in breast tumours when compared with non-neoplastic tissue, mastectomy samples were divided into 16 sectors. Multifocal tumours, of varying receptor phenotype were found in 4 patients and in addition different regions of large tumours also showed varying receptor contents. Remaining samples were found to consist of normal tissue, with fat, connective tissue and some benign breast disease. In the 9 patients with oestrogen receptor positive tumours (ER), ER content was invariably much greater in the tumours than in the remainder of the breast. Progesterone receptor (PR) content was not closely related to ER, and was lowest in the poorly differentiated tumours. This relation to differentiation was not seen in ER. The data support the view that ER concentration in ER positive tumours may reflect the transformed nature of neoplastic tissue.


Interpretive criteria and quality control guidelines for lomefloxacin and meropenem in susceptibility tests of Haemophilus influenzae using Haemophilus test medium.
Lomefloxacin and meropenem were tested in a multilaboratory study to establish susceptibility testing interpretive criteria and quality control (QC) guidelines for Haemophilus influenzae using Haemophilus test medium (HTM). Interpretive criteria were established by using triplicate testing of 102 representative H. influenzae strains. Only a susceptible category was proposed for lomefloxacin (greater than or equal to 22 mm and less than or equal to 2 micrograms/ml) and meropenem (greater than or equal to 13 mm and less than or equal to 4 micrograms/ml) due to the lack of resistant isolates. QC range for H. Influenzae ATCC 49247 were established using multiple HTM agar and broth base lots, three disk lots for each drug, and a number of test replicates consistent with the National Committee for Clinical Laboratory Standards M23-T guideline.


Serum corticosteroid-binding globulin levels in children undergoing heart surgery.
Serum corticosteroid-binding globulin (CBG) levels were measured in children (mean age 4 years) during heart surgery. Considerable decrease in CBG level occurred between baseline examination (416 +/- 39 nM) and the day of surgery (314 +/- 30 nM). Relatively simple closed heart surgery did not influence CBG level with maximal cortisol level being 20 +/- 4 micrograms/dl. Open heart surgery under conditions of profound hypothermia (26 C, without extracorporeal circulation) caused dramatic lowering of CBG level, particularly striking after resuscitation (180 +/- 20 nM). At the same time cortisol level reached extremely high values (78 +/- 8 micrograms/dl). These data suggest that CBG is likely to play an important role in pituitary-adrenal response to surgery under severe conditions of hypothermia and cardiac arrest.


Differential thermal analysis techniques as a tool for preliminary examination of catalyst for combustion.
The need for more economical catalysts for various combustion reactions is continuously driving catalyst development. We present Differential Thermal Analysis (DTA) and Differential Scanning Calorimetry (DSC) as suitable techniques for fast examination of catalyst activity for combustion reactions. The heat of reaction ΔHr generated at the catalyst in a combustible atmosphere is the measure for estimating the capability of the catalyst. Present investigations verify the reliability of both methods for the pre-selection of catalysts for further extensive investigations. To simplify the measurements and the result evaluation, a new measurement routine is introduced which is more suitable for rapid catalyst investigation than the conventional approach. For initial investigations, oxidation of 1% methane on a cobalt oxide catalyst was used. First, DTA measurements were performed. The vessel size and the amount of catalyst are considered as factors influencing the thermal signal. Simultaneous mass spectrometry measurements were used to better understand the formation of the DTA response. Comparable DSC investigations were then conducted. Finally, the behavior of catalyst was compared with two commercial palladium/alumina catalysts using DTA and DSC. Our investigations show that DTA and DSC are powerful methods to identify potential catalysts in a fast and reproducible manner, provided that all parameters influencing the thermal signal are kept constant.


Experimental data on novel Fe(III)-complexes containing phenanthroline derivatives for their anticancer properties.
This dataset is related to the research article entitled "May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticancer agents?" [1]. It includes the characterization by UV-Vis absorption spectroscopy and magnetic techniques of a group of mixed ligand Fe(III) complexes bearing a tripodal aminophenolate ligand L2-, H2L = N,N-bis(2-hydroxy-3,5-dimethylbenzyl)-N-(2-pyridylmethyl)amine, and different aromatic bases (NN = 2,2'-bipyridine [Fe(L)(bipy)]PF6 (1), 1,10-phenanthroline [Fe(L)(phen)]PF6 (2), or a phenanthroline derivative co-ligand: [Fe(L)(amphen)]NO3 (3), [Fe(L)(amphen)]PF6 (3a), [Fe(L)(Clphen)]PF6 (4), [Fe(L)(epoxyphen)]PF6 (5) (where amphen = 1,10-phenanthroline-5-amine, epoxyphen = 5,6-epoxy-5,6-dihydro-1,10-phenanthroline, Clphen = 5-chloro-1,10-phenanthroline), as well as [Fe(L)(EtOH)]NO3 (6), [Fe(phen)Cl3] (7) and [Fe(amphen)Cl3] (8). Data on their hydrolytic stability in physiological buffers is shown, as well as on their interaction with calf thymus DNA by spectroscopic tools. Additionally, the anticancer efficacy and the cellular death mechanisms activated in response to these drugs in HeLa, H1299 and MDA-MB-231 cells are provided.


Ectoparasitism as a possible cost of social life: a comparative analysis using Australian passerines (Passeriformes).
The hypothesis that cooperative breeding entails a cost in terms of transmission of ectoparasites was tested by a comparative analysis among sympatric Australian passerines. The general trend found using the allometry method and outgroup analysis indicates that contagious ectoparasites are not more common on cooperatively breeding than on non-cooperatively breeding hosts. Body weight, migratory patterns and relative abundance of hosts are factors far more important than cooperative breeding that affect the levels of ectoparasitism in the host genera studies. Ectoparasitism increases with host body weight and relative adundance, while sedentary host genera tended to show less hippoboscid fly diversity than migratory host genera. There is an interaction between breeding system and migratory pattern when relative density of contagious ectoparasites (i.e. mites, ticks and bird lice) is considered: the number of contagious ectoparasites per host is larger on cooperatively breeding host genera than on non-cooperatively breeding host genera among sedentary passerines, but the trend is reversed for migrant passerines.


Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation.
T-bet and STAT4 play critical roles in helper T cell differentiation, especially for Th1 cells. However, it is still unknown about the relative importance and redundancy of T-bet and STAT4 for Th1 differentiation. It is also unknown about their independent role of T-bet and STAT4 in the regulation of allergic airway inflammation. In this study, we addressed these issues by comparing T-bet-deficient (T-bet(-/-)) mice, STAT4(-/-) mice, and T-bet- and STAT4-double-deficient (T-bet(-/-)STAT4(-/-)) mice on the same genetic background. Th1 differentiation was severely decreased in T-bet(-/-) mice and STAT4(-/-) mice as compared with that in wild-type mice, but Th1 differentiation was still observed in T-bet(-/-) mice and STAT4(-/-) mice. However, Th1 cells were hardly detected in T-bet(-/-)STAT4(-/-) mice. In contrast, the maintenance of Th17 cells was enhanced in T-bet(-/-) mice but was reduced in STAT4(-/-) mice and T-bet(-/-)STAT4(-/-) mice. In vivo, Ag-induced eosinophil and neutrophil recruitment into the airways was enhanced in T-bet(-/-) mice but was attenuated in STAT4(-/-) mice and T-bet(-/-)STAT4(-/-) mice. Ag-induced IL-17 production in the airways was also diminished in STAT4(-/-) mice and T-bet(-/-)STAT4(-/-) mice. These results indicate that STAT4 not only plays an indispensable role in T-bet-independent Th1 differentiation but also is involved in the maintenance of Th17 cells and the enhancement of allergic airway inflammation.


Leaky-wave metasurfaces for integrated photonics.
Metasurfaces have been rapidly advancing our command over the many degrees of freedom of light; however, so far, they have been mostly limited to manipulating light in free space. Metasurfaces integrated on top of guided-wave photonic systems have been explored to control the scattering of light off-chip with enhanced functionalities-namely, the point-by-point manipulation of amplitude, phase or polarization. However, these efforts have so far been limited to controlling one or two optical degrees of freedom at best, as well as device configurations much more complex compared with conventional grating couplers. Here we introduce leaky-wave metasurfaces, which are based on symmetry-broken photonic crystal slabs that support quasi-bound states in the continuum. This platform has a compact form factor equivalent to the one of grating couplers, but it provides full command over the amplitude, phase and polarization (four optical degrees of freedom) across large apertures. We present devices for phase and amplitude control at a fixed polarization state, and devices controlling all the four optical degrees of freedom for operation at a wavelength of 1.55 μm. Merging the fields of guided and free-space optics through the hybrid nature of quasi-bound states in the continuum, our leaky-wave metasurfaces may find applications in imaging, communications, augmented reality, quantum optics, LIDAR and integrated photonic systems.


Allergic contact sensitization potential of hydroxycitronellal in humans.
Hydroxycitronellal, an important ingredient in fragrances, was studied for its sensitizing potential in human skin. Fifteen human maximization tests were conducted with hydroxycitronellal obtained from four different sources at induction concentrations from 5 to 12%. No reactions were induced at 5% in two separate panels while 10% sensitized 2/25 panelists in one test but none in a second. Induction at 12% produced sensitization in 8 of 11 tests. Impurities do not appear to be a sensitizing factor. There is some evidence that the l-stereoisomer is a less potent sensitizer than the d-stereoisomer. In an initial modified human repeat-insult patch-test two positive reactions to challenge were observed among 197 panelists, one at a concentration of 5% and the other at 7.5%. When 100 of the non-reacting panelists were re-exposed in the same way, allergic sensitization reactions appeared during the induction period with concentrations as low as 2.5%. When 28 sensitized panelists were exposed to 1% concentrations in a simulated use test, there were three reactors. A no-effect level for sensitization has not been determined although the lowest concentrations tested were in the product usage range.


Associations of rheumatoid arthritis and rheumatoid factor with mental health, sleep and cognition characteristics in the UK Biobank.
While previous rheumatoid arthritis (RA) studies have focussed on cardiometabolic and lifestyle factors, less research has focussed on psychological variables including mood and cognitive health, and sleep. Cross-sectional analyses tested for associations between RA and RF+ (positive rheumatoid factor) vs. mental health (depression, anxiety, neuroticism), sleep variables and cognition scores in UK Biobank (total n = 484,064). Those RF+ were more likely to report longer sleep duration (β = 0.01, SE = 0.004, p < 0.01) and less likely to get up in the morning easily (OR 0.95, 95% CI 0.92-0.99, p = 0.01). Those reporting RA were more likely to score higher for neuroticism (β = 0.05, SE = 0.01, p < 0.001), to nap during the day (OR 1.10, 95% CI 1.06-1.14, p < 0.001), have insomnia (OR 1.28, 95% CI 1.22-1.35, p < 0.001), have slower reaction times (β = 0.02, SE = 0.008, p < 0.005) and score less for fluid intelligence (β = - 0.03, SE = 0.01, p < 0.05) and less likely to get up easily (OR 0.61, 95% CI 0.58-0.64, p < 0.001). The current study suggests that prevalent RA, and RF+ status are associated with differences in mental health, sleep, and cognition, highlighting the importance of addressing these aspects in clinical settings and future research.


Emergency department (ED) utilization of oldest old men in a veterans care home in Taiwan.
ED is a common channel for older people to seek for medical services. However, unlike most care homes in the world, veterans care home in Taiwan has a constantly operating outpatient and inpatient services. Therefore, utilization of ED services among veterans care home may be different from most care home residents. Records of residents in Banciao Veterans Home residents visiting the ED of Taipei Veterans General Hospital from January to December of 2006 were retrospectively collected and analyzed. Demographic variables including age, sex, modes of arrival, category of triage, time of visit, main presenting symptoms, principal diagnosis, medical expenditure and the disposition after the ED visit or after admission to wards were carefully recorded. In total, 368 residents (mean age=81.9+/-5.9 years, all men) with 635 visits were identified. Nearly a half of Banciao Veterans Home residents had visited ED for at least once in 2006 and the medical expenditure was four times higher than other ED visitors. In average, 52.3% of ED visitors would be hospitalized and the most common diagnosis was infectious conditions. Onsite primary care geriatricians may play an important role in such settings.


Monoclonal antibody Daratumumab promotes macrophage-mediated anti-myeloma phagocytic activity via engaging FC gamma receptor and activation of macrophages.
Daratumumab (DAR) is novel human anti-CD38 IgG1, high-affinity human monoclonal antibody having broad-spectrum killing activity. The antibody is recommended to treat multiple myeloma. Recently Antibody-dependent cellular phagocytosis (ADCP) have been identified as the potential mechanism of DAR in addition to complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). In the present study we evaluated the effect of Daratumumab on other effector cells of multiple myeloma. Luciferase+ MM.1R GFP cells were selected for the study. For immune-compromised multiple myeloma tumour xenograft mouse model we used severe combined immunodeficient beige (SCID-beige), NOD SCID gamma (NSG) and C57Bl/6j mice. Bioluminescence imaging was carried by injecting luciferin, and in vivo confocal microscopy was done for tracing bone marrow niches. Spleen and tumours were submitted to immunophenotypic analysis. MTT assay was done for cell proliferation studies. We established tumour xenograft mouse model. It was found that DAR showed significant anti-tumour effect in tumour xenograft multiple myeloma mice. We found that DAR showed anti-tumour activity via Fc-FcγR interaction with macrophages. DAR induced phenotypic activation of macrophages in mice and resulted in ADCP of cancerous cells via interacting Fc-FcγR in vitro. The study suggested that DAR exerted anti-tumour activity in multiple myeloma by interacting with Fc-FcγR.


Resource availability, maternal effects, and longevity.
Experiments with a clone of the cladoceran Daphnia pulex indicate that the nutritional conditions of the maternal environment play a major role in determining the progeny's phenotype. Apparently, by influencing the physiology and/or morphology of individuals during early development, maternal investment not only enhances juvenile survival but has long-lasting, favorable effects on the progeny's ability to convert resources into growth and reproduction as well as negative repercussions for adult survival of the progeny. Life-span may also be radically altered by modifying food schedules within an individual's life. Neither reproductive effort nor rate of living hypotheses can explain longevity variation within Daphnia clones; rather the onset of senescence appears to be associated with a general breakdown in the ability to incorporate energy into biomass. Analysis of our results as well as earlier data with a "rate of aging-threshold vitality" model suggests that increasing the availability of food to an individual increases the rate of aging while decreasing the threshold vitality necessary for survival and that increasing maternal investment increases both the vitality at birth and the rate of aging of the progeny.


Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation.
Piperidinylpyrimidine derivatives, previously prepared as inhibitors of TNF-alpha production, were evaluated for their inhibitory activity against HIV-1 LTR activation. Some of these derivatives inhibited activation of HIV-1 LTR-directed CAT gene expression induced by PMA in Jurkat cells. In this report, we describe SAR in this series of compounds and show that the 3,4-methylenedioxybenzoyl (piperonyloyl) group on the nitrogen of piperidine and lipophilic substitution at the C(6)-position of pyrimidine are important for this inhibitory activity. Some of the synthesized compounds also inhibited HIV-1 LTR transactivation induced by viral protein Tat. These results suggest that piperidinylpyrimidines are useful as potent AIDS therapeutics that directly inhibit HIV-1 LTR activation and indirectly suppress TNF-alpha production.


Life satisfaction of older Turks living in Australia.
This study examined the influence of socio-economic and demographic variables, the frequency of travel to Turkey and years of living in Sydney on the life satisfaction of older Turkish people. This study was conducted with 110 participants of 60 years of age or older, at the New South Wales Turkish Welfare Association in Sydney, Australia. The surveys were administered face-to-face at a date and time these participants went to the Association. The dependent variable of the study was the Life Satisfaction Scale. The study data were analysed using hierarchical regression analysis, and the three sets of regression models were run for each sex. The research found that in addition to sociodemographic factors, frequency of travel to Turkey, particularly for older women, and their years of living in Sydney had negative effects on life satisfaction. The study results indicate that the frequency of both the male and female participants' visits to Turkey had a strong negative influence on their life satisfaction. Life satisfaction decreased as the frequency of the participants' visits to Turkey and years of living in Sydney increased. These findings support the current literature that shows the effects of the frequency of travel to Turkey and years of living in Sydney, which were considered to influence relationships with social networks, on life satisfaction, and indicates the necessity for a more detailed examination of social network relationships.


Impact of sphincter lesions and delayed sphincter repair on sacral neuromodulation treatment outcomes for faecal incontinence: results from a Finnish national cohort study.
The aim of this multicentre study was to analyse the effects of patent sphincter lesions and previous sphincter repair on the results of sacral neuromodulation (SNM) treatment on patients with faecal incontinence (FI). Patients examined by endoanal ultrasound (EAUS) with FI as the indication for SNM treatment were included in the study. Data was collected from all the centres providing SNM treatment in Finland and analysed for differences in treatment outcomes. A total of 237 patients treated for incontinence with SNM had been examined by EAUS. Of these patients, 33 had a history of previous delayed sphincter repair. A patent sphincter lesion was detected by EAUS in 128 patients. The EAUS finding did not influence the SNM test phase outcome (p = 0.129) or the final treatment outcome (p = 0.233). Patient's history of prior sphincter repair did not have a significant effect on the SNM test (p = 0.425) or final treatment outcome (p = 0.442). Results of our study indicate that a sphincter lesion or previous sphincter repair has no significant effect on the outcome of SNM treatment. Our data suggests that delayed sphincter repair prior to SNM treatment initiation for FI is not necessary.


Brown adipose tissue mitochondrial subpopulations show different morphological and thermogenic characteristics.
Rat brown adipose tissue mitochondrial subpopulations-isolated by differential centrifugation at 1000, 3000 and 8000g, giving the heavy, medium and light mitochondria-were characterized. Thus, contamination by non-mitochondrial subcellular components, morphological features, respiratory chain and antioxidant enzyme activities, both uncoupling protein 1 and mitochondrial protein content, mitochondrial DNA levels and mitochondrial integrity were measured. Results indicate that mitochondrial fractions showed important differences in the morphological, thermogenic and antioxidant properties. All the parameters studied were always higher in heavy mitochondria, which is indicative of a greater mitochondrial differentiation state.


A biotin-avidin labeled enzyme immunoassay for the quantitation of serum TSH using protein-layered solid phase.
A sensitive enzyme immunoassay for serum TSH has been developed utilizing the tight binding between biotin and avidin, and three layered protein polystyrene beads as solid phase. To increase binding capacity of TSH and sensitivity of the assay, the polystyrene beads were coated sequentially with mouse immunoglobulin as first layer, rabbit antimouse immunoglobulin as second layer and monoclonal anti-TSH as third layer. A serum sample was incubated simultaneously with a monoclonal anti-TSH immobilized polystyrene beads and a second monoclonal anti-TSH covalently attached to biotin. After washing, the antibody bound serum TSH-anti-TSH-biotin complex is reacted with horseradish peroxidase (HRP)-labeled avidin. Following a second wash, the bound HRP activity was measured colorimetrically. Reproducible results were obtained within 4 hours for serum TSH in the range between 0 microIU/ml and 50 microIU/ml with detection limit of 0.1 microIU per test.


Using velocity-pressure loops in the operating room: a new approach of arterial mechanics for cardiac afterload monitoring under general anesthesia.
Cardiac afterload is usually assessed in the ascending aorta and can be defined by the association of peripheral vascular resistance (PVR), total arterial compliance (Ctot), and aortic wave reflection (WR). We recently proposed the global afterload angle (GALA) and β-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta. The aim of this study was to 1) describe the arterial mechanic properties by studying the velocity-pressure relations according to cardiovascular risk (low-risk and high-risk patients) in the ascending and descending thoracic aorta and 2) analyze the association between the VP loop (GALA and β-angle) and cardiac afterload parameters (PVR, Ctot, and WR). PVR, Ctot, WR, and VP loop parameters were measured in the ascending and descending thoracic aorta in 50 anesthetized patients. At each aortic level, the mean arterial pressure (MAP), cardiac output (CO), and PVR were similar between low-risk and high-risk patients. In contrast, Ctot, WR, GALA, and β-angle were strongly influenced by cardiovascular risk factors regardless of the site of measurement along the aorta. The GALA angle was inversely related to aortic compliance, and the β-angle reflected the magnitude of wave reflection in both the ascending and descending aortas (P < 0.001). Under general anesthesia, the VP loop can provide new visual insights into arterial mechanical properties compared with the traditional MAP and CO for the assessment of cardiac afterload. Further studies are necessary to demonstrate the clinical utility of the VP loop in the operating room.NEW & NOTEWORTHY Our team recently proposed the global afterload angle (GALA) and β-angle derived from the aortic velocity-pressure (VP) loop as continuous cardiac afterload monitoring in the descending thoracic aorta under general anesthesia. However, the evaluation of cardiac afterload at this location is unusual. The present study shows that VP loop parameters can describe the components of cardiac afterload both in the ascending and descending thoracic aorta in the operating room. Aging and cardiovascular risk factors strongly influence VP loop parameters. The VP loop could provide continuous visual additional information on the arterial system than the traditional mean arterial pressure and cardiac output during the general anesthesia.


Brain magnetic resonance imaging in adults with asthma.
In individuals with asthma, potential central nervous system changes can occur as a consequence of their asthma or therapy. Clinical trials of anti-asthmatic therapies might benefit from using magnetic resonance imaging (MRI) to assess potential brain abnormalities. As part of the clinical safety evaluation of a monoclonal antibody directed against interleukin-9 for the treatment of asthma, we assessed whether brain MRI is an appropriate screening tool to evaluate potential neurotoxicity. Brain MRIs were conducted as part of a prespecified safety evaluation in adults aged 19 to 47 years with mild to moderate asthma treated with either the investigational monoclonal antibody or placebo. An independent neuroradiologist performed a blinded review of brain MRI scans obtained at baseline before dosing and day 28 after dosing from two separate clinical studies. Fifteen brain MRI abnormalities were noted in 13 of 21 subjects with asthma (62%). Nonspecific deep white matter hyperintensities (24%), perivascular space (24%), and abnormal anatomic findings (14%) were noted either at baseline or follow-up. Only 8 of 21 subjects (38%) with asthma had normal brain MRI results. The high rate of incidental brain MRI findings suggests that these abnormalities are relatively common in patients with asthma. Thus, brain MRI may not be an appropriate screening tool to evaluate potential neurotoxicity in subjects during routine clinical studies without a baseline examination. Due to artifacts simulating lesions, an experienced radiologist should interpret all brain MRI results.


Cellular proliferation and cytokine responses to polymethylmethacrylate particles in patients with a cemented total joint arthroplasty.
The in vitro response of peripheral blood mononuclear cells (MNC) from patients with cemented total hip or knee arthroplasties, and control individuals, to polymethylmethacrylate (PMMA) was assessed by cell proliferation, cytokine production, and molecular techniques. After seven days in culture, a dose-dependent proliferative response to PMMA stimulation was observed in MNC from fifteen normal individuals. A concomitant dose-dependent production of both IL-1 beta and IL-2 in response to PMMA stimulation was detected. Reverse transcription-polymerase chain reactions (RT-PCR) indicated that both IL-1 beta and IL-2 mRNA was present after 48 hours in culture with PMMA. Cellular proliferation and cytokine production (both IL-1 beta and IL-2) in 10 patients with stable, painless, well-functioning, cemented arthroplasties was significantly lower (p < 0.025) than normal controls and patients with aseptically loosened, painful, arthroplasties. The findings suggest that patients with stable cemented total joint arthroplasties are either inherently or adaptively less responsive to PMMA at a cellular level.


Combined effects of lactoperoxidase system-whey protein coating and modified atmosphere packaging on the microbiological, chemical and sensory attributes of Pike-Perch fillets.
The present study aimed to evaluate the efficacy of lactoperoxidase system-whey protein coating and modified atmosphere packaging (60% CO2, 30% N2, 10% O2) combination (LPOS + WPS + MAP) on the microbiological, chemical and sensory specifications of Pike-Perch (Sander Lucioperca, Linnaeus 1758) fillets. The highest bacterial count was observed in the fish fillets packaged with whey protein coating solutions (WPS) in compare with the other groups. Combination of WPS + LPOS and MAP packaging could significantly inhibit bacterial growth. Total volatile basic nitrogen (TVB-N), as a quality index of flesh, had strong correlation (r = 0.98-0.99) with microbial load, so that the highest and the lowest TVB-N values were observed in WPS and WPS + LPOS + MAP batches, respectively. Assessments of thiobarbituric acid reactive substances index showed that incorporation of LPOS with WPS or MAP did not have remarkable effect on lipid oxidation, but combined effect of MAP and WPS + LPOS on reducing fat oxidation was significant. The pH values in WPS + LPOS, WPS + MAP and WPS + LPOS + MAP were significantly lower than WPS. Sensory evaluations indicated that LPOS + WPS + MAP kept Pike-Perch fillets at high sensory acceptability for at least 16 days in refrigerated temperature. In conclusion, combination of MAP and WPS + LPOS showed synergistic effects on shelf-life extension of Pike-Perch fillets under refrigerated storage.


The management of paroxysmal tachycardias using the Cybertach-60.
The Cybertach-60 is a bipolar multiprogrammable pacemaker designed for the automatic detection and termination of reentrant tachycardias using bursts of rapid pacing. From August 1979 to March 1984 in the U.S.A., 143 patients received the device; 91 for supraventricular and 52 for ventricular tachycardia. After a mean follow-up period of 1.8 years, 82% of patients with supraventricular tachycardia remain alive with the implanted pacemaker providing the principal therapy for the arrhythmia. Of those patients with ventricular tachycardia, 30 (58%) remain alive (mean follow-up 1.1 years) and use the device for tachycardia termination. In this group there were 18 patient deaths: 14 documented and not sudden; 4 sudden and not documented. None of the 14 documented deaths were a result of arrhythmia or pacemaker activity. The Cybertach-60 has proved to be effective in the long-term management of patients with reentrant rhythms, particularly supraventricular tachycardia.


Molecular pathways and molecular imaging in breast cancer: an update.
Breast cancer is a heterogenic cancer being characterized by a variability of somatic mutations and in particular by different receptor expressions, such as estrogen, progesterone and human epidermal receptor. These phenotype characteristics play a crucial role in determining tumour response to various chemotherapies and other treatments and in the development of resistance to therapies. Positron emission tomography (PET) as a nuclear medicine technique, has recently demonstrated the advantages in determining the severity of disease and in evaluating the efficacy of treatments in a variety of neoplasm, including breast cancer. Because this procedure is able to pinpoint molecular activity within the body, it offers the potential to identify disease in its earliest stages as well as a patient's immediate response to therapeutic interventions in a non-invasive way. In this paper we performed an extended view about the correlation between molecular factors of breast cancer and PET tracers; in particular, we focalized our attention on their possible advantages in terms of 1) early detection of primary or recurrent cancer; 2) as a guide for target therapies and 3) for the evaluation of response to specific and now-available molecular treatments.


Public welfare crowdfunding decision-making of environmental nonprofit organizations based on social responsibility.
Sustainable crowdfunding has emerged as a significant factor in the quest for alternative funding streams in recent times. The process has entailed the removal of financial obstacles and intermediaries, facilitating proximity between entrepreneurs' initiatives and fund providers, thereby initiating modifications in conventional investment and profitability criteria. The correlation between corporate social responsibility (CSR) and sustainable business returns is a significant metric that may enhance funding costs. CSR initiatives and crowdfunding possess the potential for mutually beneficial outcomes in terms of fundraising. However, fundraisers encounter obstacles and competition in their efforts to attain their donation objectives. As an illustration, CSR endeavors may provide a chance to raise capital via crowdfunding. Conversely, crowdfunding has the potential to serve as a means of micro-funding various social initiatives that align with a corporation's corporate social responsibility objectives. The present research investigates the correlation between efficacious donation fundraising campaigns in the context of crowdfunding endeavors that hold the possibility of transforming into corporate social responsibility initiatives. The present study investigates the correlation between the initial amount of funds raised on the first day of a fundraising campaign and the target amount of funds sought by the fundraiser, as well as the type of activities involved. The present study utilizes data derived from crowdfunding endeavors in Southeast Asian nations to scrutinize the funds amassed through donations by juxtaposing trends, cultures, and characteristics of fundraisers employing donation-based crowdfunding. The present investigation employs data collected between the period spanning from the beginning of September 2021 to the end of September 2021 in the economies of Southeast Asia, including Singapore, Indonesia, Malaysia, Thailand, and the Philippines. The present investigation utilizes the partial least squares structural equation modeling (PLS-SEM) approach for the estimation of the variables. The findings of the hypothesis indicate that there exists a positive correlation between crowdfunding, environmental nonprofit organizations, organizational profitability, and CSR.


Increased interleukin-1β levels are associated with left ventricular hypertrophy and remodelling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention.
To assess the relationship between interleukin (IL)-1-related molecules, infarct size and left ventricular (LV) remodelling following acute myocardial infarction (MI). Forty-two patients with first-time diagnosis of ST segment elevation MI (STEMI), with a single occluded vessel successfully revascularized by primary percutaneous coronary intervention (PCI), were recruited to this observational study conducted at a university teaching hospital and followed for 1 year. Plasma levels of IL-1β, IL-1 receptor antagonist (IL-1Ra), IL-18 and caspase-1 were analysed before and 2 days, 1 week and 2 months after PCI. Serial cardiac magnetic resonance imaging (CMR) was used for the assessment of infarct size and LV remodelling. CMR findings at 1 year was the primary outcome variable. Univariate analysis showed that IL-1-related mediators were strongly (IL-1 β), moderately (caspase-1) and weakly (IL-1Ra) associated with impaired myocardial function and noninfarct mass, but not infarct size, 1 year after reperfused STEMI. In multivariate analyses, troponin T predicted LV ejection fraction (LVEF), infarct size and LV end-diastolic (LVEDVi) and end-systolic volume index (LVESVi). However, significant additional variance was explained by IL-1β, IL-18 and caspase-1. IL-1β levels at 2 months, IL-18 at 2 days and pre-PCI caspase-1 were predictors of LVEF. Caspase-1 and in particular IL-1β at 2 days were the only predictors of noninfarct mass. IL-1β and IL-18 at 2 days were predictors of LVEDVi, whilst pre-PCI levels of IL-1β contributed to prediction of LVESVi. By contrast, pro-B-type natriuretic peptide, C-reactive protein, IL-6 and transforming growth factor-β1 (TGF-β1) had no or only a weak (TGF-β1) association with these CMR parameters in multivariate analyses. IL-1β levels after STEMI were strongly associated with impaired myocardial function and noninfarct LV mass after 1 year, suggesting a potential role for IL-1β as a predictor of maladaptive myocardial remodelling following reperfused MI.


Organised cervical cancer screening still leads to higher coverage than spontaneous screening in The Netherlands.
In The Netherlands, early detection of cervical cancer by programme and spontaneous screening has been common practice for more than two decades. Both types of screening are mainly performed by general practitioners. Therefore, the question is raised of whether programme screening still enhances screening uptake. To answer this question, we analysed the national health interview survey in the years 1992-1996. The coverage rate, defined as the percentage of women with at least one smear taken in the previous 5 years, was 91% for women invited for programme screening compared with 68% for women not invited. The performance of the organised programme in reducing excessive screening, i.e. smears taken in excess of the recommended age and interval range, was not clear and the effect seemed small. Furthermore, we found that half the non-attenders were 'protected' by a recent smear or a hysterectomy, and of the unprotected women, 72% showed a positive attitude towards the programme. We conclude that even after a long history of cervical cancer screening, an organised programme is still required to ensure a high coverage.


Clinicopathological analysis of malignant eyelid tumor cases at Yamagata university hospital: statistical comparison of tumor incidence in Japan and in other countries.
To report the clinical and histopathological features of malignant eyelid tumor cases treated in our clinic. We also compared the differences in the frequency of malignant eyelid tumor in various regions of Japan and worldwide. Retrospectively, we studied the records of the 38 cases of malignant eyelid tumor treated in Yamagata University Hospital over the last 17 years. The statistical comparison with various countries was based on reports of case studies in those countries. Data from our clinic: Among the total of 38 cases, 15 cases (39.5%) were diagnosed as basal cell carcinoma, 11 cases (28.9%) as sebaceous gland carcinoma, and 4 cases (10.5%) as squamous cell carcinoma. In addition, three cases were malignant melanoma, two adenocarcinoma, one Merkel cell carcinoma, one malignant peripheral nerve sheath tumor, and one malignant lymphoma. The ages of patients ranged from 45 to 92 years (mean, 72.0 +/- 12.4 years). Most of the cases were treated by complete resection of the tumors and eyelid reconstruction. Radiation or cryotherapy were added when required. The prognosis of the cases with basal cell carcinoma and squamous cell carcinoma was good, and that of the other tumors was relatively poor. During the same period, in Caucasians, basal cell carcinoma constituted about 80%-90% of the malignant eyelid tumors, whereas in Japan and Asian countries, basal cell carcinoma, sebaceous gland carcinoma, and squamous cell carcinoma each constituted about 20%-40%. A racial difference in the incidence of basal cell carcinoma, sebaceous gland carcinoma, and squamous cell carcinoma can be considered in making a diagnosis.


Prediction of methylated CpGs in DNA sequences using a support vector machine.
DNA methylation plays a key role in the regulation of gene expression. The most common type of DNA modification consists of the methylation of cytosine in the CpG dinucleotide. At the present time, there is no method available for the prediction of DNA methylation sites. Therefore, in this study we have developed a support vector machine (SVM)-based method for the prediction of cytosine methylation in CpG dinucleotides. Initially a SVM module was developed from human data for the prediction of human-specific methylation sites. This module achieved a MCC and AUC of 0.501 and 0.814, respectively, when evaluated using a 5-fold cross-validation. The performance of this SVM-based module was better than the classifiers built using alternative machine learning and statistical algorithms including artificial neural networks, Bayesian statistics, and decision trees. Additional SVM modules were also developed based on mammalian- and vertebrate-specific methylation patterns. The SVM module based on human methylation patterns was used for genome-wide analysis of methylation sites. This analysis demonstrated that the percentage of methylated CpGs is higher in UTRs as compared to exonic and intronic regions of human genes. This method is available on line for public use under the name of Methylator at http://bio.dfci.harvard.edu/Methylator/.


An empirical assessment of baseline feature location techniques.
Feature Location (FL) aims to locate observable functionalities in source code. Considering its key role in software maintenance, a vast array of automated and semi-automated Feature Location Techniques (FLTs) have been proposed. To compare FLTs, an open, standard set of non-subjective, reproducible "compare-to" FLT techniques (baseline techniques) should be used for evaluation. In order to relate the performance of FLTs compared against different baseline techniques, these compare-to techniques should be evaluated against each other. But evaluation across FLTs is confounded by empirical designs that incorporate different FL goals and evaluation criteria. This paper moves towards standardizing FLT comparability by assessing eight baseline techniques in an empirical design that addresses these confounding factors. These baseline techniques are assessed in twelve case studies to rank their performance. Results of the case studies suggest that different baseline techniques perform differently and that VSM-Lucene and LSI-Matlab performed better than other implementations. By presenting the relative performances of baseline techniques this paper facilitates empirical cross-comparison of existing and future FLTs. Finally, the results suggest that the performance of FLTs partially depends on system/benchmark characteristics, in addition to the FLTs themselves.


Comparison of cost-effectiveness between the quantiFERON-TB Gold-In-Tube and T-Spot tests for screening health-care workers for latent tuberculosis infection.
There are several methods used to screen for latent tuberculosis (TB) infection (LTBI) including the QuantiFERON-TB Gold-in-Tube (QFT-GIT) and T-SPOT-TB (T-SPOT) tests. Many studies have reported the equivalence of these two methods, but it is unclear which of them is more cost effective. We investigated the age and cost issues of these tests in screening for LTBI among health-care workers. One hundred and forty new employees during 2008-2011 in our hospital were screened using the QFT-GIT test, and 140 new employees during 2011-2014 were screened with the T-SPOT test for LTBI. The results of both tests were classified as positive, undetermined (retesting required), or negative. There were six positive results (4.29%), eight undetermined results (5.71%), and 126 negative results (90.0%) with the QFT-GIT test. As for the T-SPOT test, there were eight positive results (5.71%), three undetermined results (2.14%), and 129 negative results (92.1%). Fourteen LTBI employees (6 in QFT-GIT and 8 in T-SPOT) were detected statistically equally using the two methods (P = 0.79). The total costs, including those incurred for retesting, were $7,711.86 (US dollar) and $6,525.42 for the QFT-GIT and T-SPOT tests (cost of one test is $55.08 for QFT-GIT and $46.61 for T-SPOT), respectively. T-SPOT is one of the options for screening for LTBI partly owing to the viewpoint of cost-effectiveness. Further prospective studies need to be considered for a definitive conclusion.


The role of adenotonsillectomy in the treatment of primary nocturnal enuresis in children: A systematic review.
Primary nocturnal enuresis (PNE) is a challenging condition for physicians, patients and families. Although the etiology remains unclear, sleep-disordered breathing (SDB) and sleep apnea have been suggested to play an important role. Recent research has suggested a potential therapeutic benefit of adenotonsillectomy (T&A) and surgical management of upper airway obstruction in the treatment of PNE. The aim was to conduct a systematic review of relevant literature to determine the effectiveness of T&A in treating children aged 2-19 years with PNE. This was a systematic review using a comprehensive electronic search strategy that included PubMed, Embase, CINAHL, Cochrane Library, conference proceedings, and the gray literature up to July 2015. We included all studies of children aged 2-19 years with PNE and SDB who underwent T&A. The primary outcome was resolution of PNE following surgery. Observational studies and randomized trials were reviewed. Risk of bias assessment and meta-analyses of included studies were performed. We screened 3254 citations; following title and abstract screening, 42 studies were selected for full-text screening by two independent reviewers. We included 18 studies (890 patients) in our final analysis. All studies were observational and only one included a control group. Meta-analysis of proportions of all (18) studies revealed a pooled complete resolution rate of 51% (43-60%), with significant heterogeneity among studies (I2 = 82.2%). Partial resolution was seen in 20% (14-27%), with similar heterogeneity to the complete resolution group. Sensitivity analysis including only studies with a low risk of bias and with patients ≥5 years (n = 244 patients) yielded a complete resolution rate of 43% (36-49%) with minimal heterogeneity (I2 = 0%; figure). In our systematic review, T&A resulted in improvement of nocturnal enuresis in more than 60% of patients, with complete resolution rates in excess of 50%. Findings were persistent on meta-analysis focused only on studies including older patients (≥5 years) and those with short follow-up after surgery (≤3 months), which imply a higher cure rate than would be expected based on natural history alone. The limitations of this review include the lack of controlled trials, the overall quality of the evidence reviewed and the heterogeneity between included studies. The role for systematic investigation and treatment of sleep disorders in patients with PNE should be scrutinized further, since a near 50% complete resolution rate for PNE may be expected with T&A in some settings.


Near infrared in and out: Deep imaging for scrap leather induced autophagy in vivo by an ultrasensitive two-photon polarity probe.
As one of the important means for eukaryotic cells to maintain homeostasis, autophagy allows for transporting deformed biomacromolecules and damaged organelles to lysosome for digestion and degradation. The process of autophagy entails the merging of autophagosomes and lysosomes, culminating in the breakdown of biomacromolecules. This, in turn, leads to a change in lysosomal polarity. Therefore, fully understanding the changes of lysosomal polarity during autophagy is of significance to the study of membrane fluidity and enzymatic reaction. However, the shorter emission wavelength has greatly damaged the imaging depth, thus seriously limiting its biological application. Therefore, in this work, a near infrared in and out lysosome-targeted polarity-sensitive probe NCIC-Pola was developed. The fluorescence intensity of NCIC-Pola showed an approximate 1160-fold increase when the polarity decreased under two-photon excitation (TPE). In addition, the excellent fluorescence emission wavelength (692 nm) enabled the deep imaging analysis of scrap leather induced autophagy in vivo.


Explanatory model of symptoms of stress, anxiety and depression in the general population: Cross-sectional study during the COVID-19 pandemic.
COVID-19 pandemic has had a great impact worldwide, specially affecting mental health and has undoubtedly taken part in human behaviour modification, increasing global health burden and with stress, anxiety and depression being the main contributors to this load. Because of the importance of this issue, the objective of this study was the creation of an explanatory model for the causal relationship of the main psychological variables: stress, anxiety and depression in the COVID-19 pandemic context. A cross-sectional study was carried out with a sample of 709 volunteers, sociodemographic variables and psychological symptoms were measured through a virtual DASS-21 questionnaire, during the COVID-19 pandemic, dated from November 2 to 6, 2020. A structural equation model using the weighted least squares means and the adjusted variance was employed for the creation and adjustment of the explanatory relational model. The results showed the presence of stress, anxiety and depression symptoms among the general population. The model showed an adequate fit (CFI = 0.94; TLI = 0.94; RMSEA = 0.06; P = 0.000) and was able to explain more than 80% of depressive symptoms (R2 = 0.86) and more than 70% of anxiety symptoms (R2 = 0.72), in addition to showing a unidirectional causal relationship of long-term stress on anxiety, and anxiety on depressive symptoms, showing a linked behaviour of the same, in the adjusted model. It was also outlined that this model was characterized by being expressed mainly in women, with lower quality of sleep and at a younger age.


Commonly reported negative experiences on social media are associated with poor mental health and well-being among adolescents: results from the "LifeOnSoMe"-study.
Cyberbullying has been extensively studied and is associated with adverse mental health outcomes in adolescents. However, adolescents may also experience a range of other negative experiences, such as name-calling, threats, exclusion, and unwanted attention or contact from others. Few studies have investigated how adolescents' mental health is affected by these relatively common and less severe types of negative experiences on social media (SOME). To assess the association between mental health outcomes and two aspects of negative experiences on SOME; unwanted attention and negative acts and exclusion. This study is based on a survey conducted in 2020/21 consisting of 3,253 Norwegian adolescents (56% female, Mage = 17 years). Eight statements about negative experiences on SOME were asked and combined into two composite measures: "Unwanted attention from others" and "Negative acts and exclusion." Dependent variables in regression models were symptoms of anxiety, symptoms of depression, and mental well-being. Covariates in all models included age, gender, subjective socioeconomic status, and amount of SOME-use. Both "negative acts and exclusion" and "unwanted attention from others" on SOME were consistently positively associated with self-reported symptoms of depression and anxiety, and negatively associated with mental well-being in both crude and adjusted analysis. The results are indicative of an important relationship between experiencing negative events on SOME, even presumably less severe events, and worse mental health and well-being. Future research should extricate the potential causal relationship between negative experiences on SOME and mental health, as well as exploring potential precipitating and intermediating factors.


Influence of cage geometry on sagittal alignment in instrumented posterior lumbar interbody fusion.
Retrospective radiographic evaluation of the sagittal alignment of the lumbar spine in patients undergoing short-segment instrumented posterior lumbar interbody fusion with cage systems of different shape. To determine whether rectangular and wedge-shaped cages have a different influence on the sagittal alignment of the lumbar spine in patients undergoing short-segment instrumented posterior lumbar interbody fusion. Previous studies of sagittal alignment after posterior lumbar interbody fusion have focused on the impact of intraoperative patient, hip, and knee positioning, as well as instrumentation characteristics on sagittal posture. The influence of the cage shape on indexes of total and segmental sagittal alignment of the lumbar spine is yet unknown. Forty-two patients having undergone instrumented short-segment posterior lumbar interbody fusion were reviewed retrospectively. Twenty-two patients (12 women and 10 men, 38-78 years of age) had posterior lumbar interbody fusion with rectangular cages. The fused segments were: 4 at L3-L4, 16 at L4-L5, 11 at L5-S1. Thirteen patients had single- and nine patients double-level fusion. Twenty patients (8 women and 12 men, 34-81 years of age) had posterior lumbar interbody fusion with wedge-shaped cages. The fused segments were: 4 at L3-L4, 15 at L4-L5, 11 at L5-S1. Ten patients had single- and 10 patients double-level fusion. Cages were packed with cancellous bone from the posterior iliac crest and/or bone fragments harvested by laminectomy. All patients had additional pedicle screw fixation. Pre- and postoperative standing lateral radiographs were assessed for segmental and lumbar lordosis as well lumbar and sacral tilt. Data were analyzed with repeated measures analysis of variance. RESULTS The mean follow-up period was 18 months with a minimum follow-up period of 14 months. Mean segmental lordosis of the fused segments showed significant changes between the two implant groups (P < 0.05). Segmental lordosis decreased in the rectangular cage group from 10 degrees to 2 degrees at L3-L4, from 10 degrees to 5 degrees at L4-L5, and from 9 degrees before to 6 degrees after fusion surgery at L5-S1. In the wedge-shaped cage group, segmental lordosis increased from 4 degrees to 7 degrees at L3-L4, from 2 degrees to 8 degrees at L4-L5, and from 9 degrees to 17 degrees at L5-S1. Analysis of changes in lumbar lordosis and lumbar and sacral tilt did not show significant differences though opposite trends: lumbar lordosis decreased from 55 degrees to 48 degrees in the rectangular cage group and increased from 45 degrees to 53 degrees in the wedge-shaped cage group. Lumbar tilt measured 98 degrees before and 102 degrees after surgery in the rectangular cage group and 97 degrees before and 94 degrees after surgery. Sacral tilt measured 44 degrees before and 40 degrees after surgery in the rectangular cage group and measured 42 degrees before and 45 degrees after surgery in the wedge-shaped cage group. The cage geometry has a significant impact on the alignment of the lumbar spine after instrumented posterior lumbar interbody fusion. With rectangular cages, lumbar lordosis and segmental lordosis of the segments fused decrease; sagittal balance is maintained by compensatory changes of the sacral tilt. Wedge-shaped cages significantly increase segmental lordosis, enhance lumbar lordosis, and therefore should be preferred for restoring sagittal alignment in instrumented posterior lumbar interbody fusion procedures.


Effects of a dopamine D3 receptor ligand, BP 897, on acquisition and expression of food-, morphine-, and cocaine-induced conditioned place preference, and food-seeking behavior in rats.
The present study addressed the role of dopaminergic D(3) receptors (D(3)R) in motivational processes in rats. The effects of the selective D(3)R partial agonist, BP 897 (0.25-1 mg/kg, i.p.), on the establishment and the expression of conditioned place preference (CPP) supported by food, morphine (4 mg/kg, s.c.), or cocaine (2 mg/kg, s.c.) were investigated using an unbiased, one-compartment, place-conditioning procedure. When administered alone, BP 897 (0.05-2 mg/kg, i.p.) did not support CPP; on the contrary, conditioned place avoidance (CPA) was observed at 1 mg/kg, suggesting that this dose of BP 897 could be perceived as aversive. When given before each cocaine injection during the conditioning phase, BP 897 (1 mg/kg) prevented the establishment of CPP, and a single administration of BP 897 (0.5 and 1 mg/kg) before the test session impaired the expression of cocaine CPP. In contrast, neither the establishment nor the expression of food- and morphine-CPP were significantly altered by BP 897 (up to 1 mg/kg), whereas the full but less selective D(3)/D(2)R agonists, 7-OH-DPAT (0.5-2 mug/kg, s.c.) and quinelorane (1 mug/kg, s.c.), prevented the acquisition of food CPP. In a within-session extinction schedule of lever pressing for food, BP 897 (0.06-2 mg/kg) was ineffective in potentiating response reinstatement induced by the noncontingent delivery of two food pellets, in contrast with quinelorane and 7-OH-DPAT where previous studies showed to be efficient in this respect (Duarte et al, 2003). These results indicate that BP 897 has no positive appetitive value on its own, and that a moderate degree of stimulation of D(3)R is not sufficient to modulate food-primed food-seeking behavior or alter incentive motivation for food, morphine, and/or their associated cues. However, D(3)R are likely involved in the perception of the rewarding value of cocaine and cocaine-paired cues. This suggests that the appetitive effects of cocaine are subserved by mechanisms different, at least in part, from those of morphine and food, and that D(3)R play a role only in the former.


Influence of Early Lactation Assistance on Inpatient Exclusive Breastfeeding Rates.
Human milk feeding reduces the incidence and costs of several maternal and childhood illnesses. Initiation and success of human milk feeding are influenced by race, socioeconomic status, and family support. The influence of early in-hospital lactation assistance in breastfeeding success has been not well described. We aimed to determine how suspected known factors influencing breastfeeding success influence in-hospital human milk feeding rates. Second, we aimed to examine how timing of lactation assistance is related to success of human milk feeding during the newborn hospitalization for healthy infants. We conducted a retrospective cohort study of term infants born between January 1, 2014 and December 31, 2016 at a large tertiary academic hospital. We considered "success" to be 100% human milk feeding during the birth hospitalization, and compared differences in success by demographics, payor, race, and initial feeding preference. Influences of lactation assistance on success were analyzed using multivariable logistic regression. Mean success with exclusive human milk feeding among 7,370 infants was 48.9%, (n = 3,601). Successful participants were more likely to be 39-40 weeks' gestation (64.9%, n = 2,340), non-Hispanic/non-Latino (80.0%, n = 2,882), and using private insurance (69.2%, n = 2,491). Participants who had early feeding assisted by an International Board Certified Lactation Consultant (IBCLC) before being fed any formula were more likely to be successful than participants who had a feeding assisted by a non-IBCLC nurse (80% vs. 40% respectively). Success for exclusive human milk feeding during newborn hospitalization is strongly associated with several factors. Early intervention with IBCLCs can greatly improve breastfeeding success.


Correction to: Photobiomodulation by dual-wavelength low-power laser effects on infected pressure ulcers.
The author name Maria Maria Côrtes Thomé Lima was incorrectly captured in the original article. The correct author name should be Andrezza Maria Côrtes Thomé Lima. The original article has been corrected.


Implementation of the Confusion Assessment Method for Noncritically Ill Adult Patients.
Several hospital interventions increase patient risk for developing delirium, including mechanical ventilation, monitoring devices, medication interactions, urinary catheters, interrupted sleep cycles, and use of physical restraints. Developing delirium leads to increased length of hospital stay, likelihood of requiring long-term care services after discharge, and risk of mortality following hospitalization. Longer periods of delirium worsen cognition, executive functioning, ability to complete activities of daily living, and sensorimotor functioning. Routine screening and early recognition prevent or reduce the long-term health and financial effects of delirium. The Confusion Assessment Method is a useable tool for screening noncritically ill adult patients for delirium.


Urinary prostaglandins in hyperglycaemic ketoacidosis of type I diabetes mellitus.
Urinary excretion of various renal prostaglandins was measured by radioimmunoassay and gas chromatography-mass spectrometry in children who had different degrees of metabolic control. Excretion in PGE2 in diabetic children was twice control values irrespective of the presence or absence of diabetic ketoacidosis (DKA). The urinary excretion of PGF2 alpha was significantly increased in diabetic children with ketoacidosis, but not when diabetes was well controlled. The excretion of 13, 14 dihydro-15-keto PGE2, the major metabolite of circulating PGE2, was increased in all diabetic children, and was most elevated in ketoacidosis when it averaged 10 times basal excretion. Urinary excretion of PGF2 alpha and of 6-keto-PGF1 alpha, the metabolite of PGI2, was approximately doubled in DKA compared with values from healthy subjects. Excretion of PGE2 was twice control values in children with stable diabetes, whereas the equivalent value for TXB2, the metabolite of the active vasoconstrictor TXA2, was reduced by approximately 50%. We suggest that the increased excretion of prostacyclin metabolite may result from a protective biological action on the kidney opposing other vasoconstrictor hormone activity. PGE2 appears not to be involved in this process. The highly elevated excretion of PGE2 metabolite may represent an activation of systemic PGE metabolism during DKA.