PSA time to nadir as a prognostic factor of first-line docetaxel treatment in castration-resistant prostate cancer: evidence from patients in Northwestern China.
Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN <17 weeks (42.83 vs 21.50 weeks, P < 0.001). The time to PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was <17 weeks. We found several factors to be associated with OS, including TTN (hazard ratio [HR]: 3.937, 95% confidence interval [CI]: 1.502-10.309, P = 0.005), PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [<0 response] compared to Class 2 [0-50% response], HR: 3.978, 95% CI: 1.278-12.387, P = 0.017). In conclusion, TTN of PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.


Clinically relevant microRNAs in ovarian cancer.
microRNAs (miRNAs/miRs) belong to a class of small noncoding RNAs that can negatively regulate messenger RNA (mRNA) expression of target genes. miRNAs are involved in multiple aspects of ovarian cancer cell dysfunction and the phenotype of ovarian cancer cells can be modified by targeting miRNA expression. miRNA profiling has detected a number of candidate miRNAs with the potential to regulate many important biologic functions in ovarian cancer, but their role still needs to be clarified, given the remarkable heterogeneity among ovarian cancers and the context-dependent role of miRNAs. This review summarizes the data collected from The Cancer Genome Atlas (TCGA) and several other genome-wide projects to identify dysregulated miRNAs in ovarian cancers. Copy number variations (CNVs), epigenetic alterations, and oncogenic mutations are also discussed that affect miRNA levels in ovarian disease. Emphasis is given to the role of particular miRNAs in altering expression of genes in human ovarian cancers with the potential to provide diagnostic, prognostic, and therapeutic targets. Particular attention has been given to TP53, BRCA1/2, CA125 (MUC16), HE4 (WFDC2), and imprinted genes such as ARHI (DIRAS3). A better understanding of the abnormalities in miRNA expression and downstream transcriptional and biologic consequences will provide leads for more effective biomarkers and translational approaches in the management of ovarian cancer.


Treatment of thoracolumbar fracture.
The most common fractures of the spine are associated with the thoracolumbar junction. The goals of treatment of thoracolumbar fracture are leading to early mobilization and rehabilitation by restoring mechanical stability of fracture and inducing neurologic recovery, thereby enabling patients to return to the workplace. However, it is still debatable about the treatment methods. Neurologic injury should be identified by thorough physical examination for motor and sensory nerve system in order to determine the appropriate treatment. The mechanical stability of fracture also should be evaluated by plain radiographs and computed tomography. In some cases, magnetic resonance imaging is required to evaluate soft tissue injury involving neurologic structure or posterior ligament complex. Based on these physical examinations and imaging studies, fracture stability is evaluated and it is determined whether to use the conservative or operative treatment. The development of instruments have led to more interests on the operative treatment which saves mobile segments without fusion and on instrumentation through minimal invasive approach in recent years. It is still controversial for the use of these treatments because there have not been verified evidences yet. However, the morbidity of patients can be decreased and good clinical and radiologic outcomes can be achieved if the recent operative treatments are used carefully considering the fracture pattern and the injury severity.


Fluoroquinolone resistance in Streptococcus dysgalactiae subsp. equisimilis and evidence for a shared global gene pool with Streptococcus pyogenes.
Quinolone resistance is an emerging problem in Streptococcus pyogenes, and recombination with Streptococcus dysgalactiae DNA has been implicated as a frequent mechanism leading to resistance. We have characterized a collection of S. dysgalactiae subsp. equisimilis isolates responsible for infections in humans (n = 314) and found a high proportion of levofloxacin-resistant isolates (12%). Resistance was associated with multiple emm types and genetic lineages, as determined by pulsed-field gel electrophoretic profiling. Since we could not find evidence for a role of efflux pumps in resistance, we sequenced the quinolone resistance-determining regions of the gyrA and parC genes of representative resistant and susceptible isolates. We found much greater diversity among the parC genes (19 alleles) than among the gyrA genes (5 alleles). While single mutations in either GyrA or ParC were sufficient to raise the MIC so that the strains were classified as intermediately resistant, higher-level resistance was associated with mutations in both GyrA and ParC. Evidence for recombination with S. pyogenes DNA was found in some parC alleles, but this was not exclusively associated with resistance. Our data support the existence of a common reservoir of genes conferring quinolone resistance shared between S. dysgalactiae subsp. equisimilis and S. pyogenes, while no recombination with the animal pathogen S. dysgalactiae subsp. dysgalactiae could be found.


Performance on the Mini-Mental State Examination and Mattis Dementia Rating Scale among older American Indians.
Optimal methods for assessing cognitive impairment among older American Indians have not been established. This study sought to examine the cultural relevance and performance of two common cognitive screening measures, the Mini-Mental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS), in one American Indian population. One hundred forty American Indians ages 60 to 89 were assessed; nearly 11% scored more than 2 standard deviation points below performance expectations on the MMSE, as did 27% to 81% on the MDRS. Complex relationships were found between gender, health conditions (with possible effects on cognitive functioning), and MMSE and MDRS scores. The authors discuss implications and future directions.


Aspirin inhibits p44/42 mitogen-activated protein kinase and is protective against hypoxia/reoxygenation neuronal damage.
Acetylsalicylic acid (ASA) is preventive against stroke and protects against focal brain ischemia in rats. We studied the mechanisms of the manner in which ASA provides neuroprotection against hypoxia/reoxygenation (H/R) injury. Spinal cord cultures exposed to 20 hours of hypoxia followed by reoxygenation were treated with a vehicle, ASA or inhibitors of inducible nitric oxide synthase (iNOS), mitogen-activated protein kinases p38 MAPK and ERK1/2, or an N-methyl-d-aspartic acid (NMDA) receptor antagonist. Cell viability was assessed by LDH release measurement and cell counts. Prostaglandin production was measured by enzyme immunoassay, MAPK signaling by immunoblotting, and DNA binding of nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) by electrophoretic mobility shift assay. One to 3 mmol/L ASA inhibited H/R-induced neuronal death when present during H/R but not when administered only for the reoxygenation period. Prostaglandin E2 production was very low and was not altered by ASA. The AP-1 and NF-kappaB DNA binding activities increased after H/R. ASA increased the H/R-induced AP-1 binding but had no effect on NF-kappaB binding. H/R induced a sustained ERK1/2 activation followed by neuronal death, whereas no changes in p38 or c-Jun N-terminal kinase were detected. ASA strongly inhibited this ERK1/2 activation. PD98059, an ERK1/2 inhibitor, was also neuroprotective, prevented H/R-induced ERK1/2 activation, and had no effect on NF-kappaB binding activity. Inhibition of NMDA receptors, iNOS, or p38 MAPK did not provide neuroprotection. Inhibition of the sustained activation of ERK1/2 may partially contribute to neuroprotection achieved by ASA against H/R injury.


[Serologic screening for hepatitis B in health professionals in the city of Goiânia-Goiás].
Markers for hepatitis B virus in health care workers were analysed in 625 employees of three institutions in Goiânia city. The virus prevalence was 23.4% related to different markers (AgHBs, anit-HBs and anti-HBc). Among the positive individuals, 1.3% presented acute infection, 1.0% were virus carriers and 21.1% presented only anti-HBs and 32.6% only anti-HBc as markers. There were 19 reports of virus vaccination. Eight of them seroconverted for anti-HBs and 6 were positive for both anti-HBc and anti-HBs. Higher prevalence rates were found above 30 year of age (p < 0.05). The male and female prevalence rates were 29.5% and 21.1% (p < 0.05) respectively. The virus prevalence rates among blood and patient contacts were 25.9% (p < 0.05) and the highest prevalence was found in persons followed up for at least ten years (p < 0.05). The greatest risk section has shown to be hemodialysis unit personnel with a percentual of 77% (p < 0.05).


DNA flow cytometry in primary breast carcinoma.
DNA Flow cytometric values were recorded in 66 primary breast carcinomas. Twenty-six tumors were found to be diploid whereas 40 were non-diploid. About 10% of the cells belonged to the S-phase fraction. Non-diploid tumors had significantly larger S-cell fractions (greater than 10%) than diploid ones. High tumor ploidy correlated positively with high clinical stage (stage I versus stage greater than or equal to II) and with high histological grade but was unrelated to estrogen-receptor content and menopausal status.


Electrokinetic characteristic and coagulation behavior flocculant polyaluminum silicate chloride (PASiC).
The electrokinetic characteristics and coagulation behaviors of polyaluminum silicate chloride (PASiC) and polyaluminum chloride (PAC) were studied and compared by streaming current (SC) measurement and jar test method. The experimental results showed that the interaction between polysilicic acid characterized negative charge and hydrolyzed aluminum species result in a decrease of the charge-neutralizing ability of PASiC, compared to PAC. The decrease has a close relationship with the basicity (B) and Al/Si molar ratio in PASiC. The less the B value and the Al/Si molar ratio, the lower the charge-neutralizing ability of PASiC is. In contrast, the preparation technique for PASiC affects the charge - neutralization of PASiC to a smaller extent. In addition, compared with PAC, PASiC may enhance aggregating efficiency and give better coagulating effects.


SecA mediates cotranslational targeting and translocation of an inner membrane protein.
Protein targeting to the bacterial plasma membrane was generally thought to occur via two major pathways: cotranslational targeting by signal recognition particle (SRP) and posttranslational targeting by SecA and SecB. Recently, SecA was found to also bind ribosomes near the nascent polypeptide exit tunnel, but the function of this SecA-ribosome contact remains unclear. In this study, we show that SecA cotranslationally recognizes the nascent chain of an inner membrane protein, RodZ, with high affinity and specificity. In vitro reconstitution and in vivo targeting assays show that SecA is necessary and sufficient to direct the targeting and translocation of RodZ to the bacterial plasma membrane in an obligatorily cotranslational mechanism. Sequence elements upstream and downstream of the RodZ transmembrane domain dictate nascent polypeptide selection by SecA instead of the SRP machinery. These findings identify a new route for the targeting of inner membrane proteins in bacteria and highlight the diversity of targeting pathways that enables an organism to accommodate diverse nascent proteins.


[Solid focal lesions in the lungs as first sign of hypereosinophilic syndrome].
The paper introduces a case of 50 years old women who was diagnosed because of solid focal lesions in the lungs with coexist hypereosinophilia in blood smear. During diagnostics neoplastic and infectious diseases were excluded. In the meanwhile secondary causes of hypereosinophilia was not found. The diagnosis of the hypereosinophilic syndrome was diagnosed and atypical (solid) character of focal lesions in the lungs was underlined.


Evaluation of Activity of Zinc Oxide Nanoparticles on Human Rotavirus and Multi-Drug Resistant Acinetobacter Baumannii.
Rotaviruses are the cause of acute gastroenteritis and severe diarrheal diseases in children worldwide. Children under the age of five are more susceptible to rotavirus infections. Due to such as the lack of effective drugs and supportive therapy only, the development of new antiviral agents against rotaviruses is required. Multi-drug-resistant Acinetobacter baumannii is also one of the most challenging Gram-negative bacteria to control and treat due to its antibiotic resistance, particularly in intensive care units. This study aimed to investigate the activity of zinc oxide nanoparticles against human rotavirus and multi-drug resistant Acinetobacter baumannii. The standard 50% tissue culture infectious dose method and the real-time polymerase chain reaction assay were used to investigate the effects of zinc oxide nanoparticles on rotaviruses. The well diffusion and the minimum inhibitory concentration method were used to assess the antibacterial activity of zinc oxide nanoparticles against Acinetobacter baumannii. 300 μg/ml of zinc oxide nanoparticles demonstrated the highest anti-rotavirus effects, resulting in a 3.16 logarithmic decrease in virus infectious titer, and a four-unit increase in the cycle threshold value of the real-time polymerase chain reaction assay compared to the untreated control (P value <0.001 and P value = 0.005, respectively). The diameter of the inhibition zone of zinc oxide nanoparticles solution against Acinetobacter baumannii was 17 mm. The minimum inhibitory concentration results of the zinc oxide nanoparticles solution against Acinetobacter baumannii was 1.56 mg/ml. Our findings showed that zinc oxide nanoparticles could be considered a promising antimicrobial compound.


Dynamic correlations between heart and brain rhythm during Autogenic meditation.
This study is aimed to determine significant physiological parameters of brain and heart under meditative state, both in each activities and their dynamic correlations. Electrophysiological changes in response to meditation were explored in 12 healthy volunteers who completed 8 weeks of a basic training course in autogenic meditation. Heart coherence, representing the degree of ordering in oscillation of heart rhythm intervals, increased significantly during meditation. Relative EEG alpha power and alpha lagged coherence also increased. A significant slowing of parietal peak alpha frequency was observed. Parietal peak alpha power increased with increasing heart coherence during meditation, but no such relationship was observed during baseline. Average alpha lagged coherence also increased with increasing heart coherence during meditation, but weak opposite relationship was observed at baseline. Relative alpha power increased with increasing heart coherence during both meditation and baseline periods. Heart coherence can be a cardiac marker for the meditative state and also may be a general marker for the meditative state since heart coherence is strongly correlated with EEG alpha activities. It is expected that increasing heart coherence and the accompanying EEG alpha activations, heart brain synchronicity, would help recover physiological synchrony following a period of homeostatic depletion.


Haematocrit levels and anaemia in Australian children aged 1-4 years.
The aim of this study was to describe the prevalence of anaemia, mean haematocrit levels, and the risk factors influencing haematocrit in participants of the 1995 National Survey of Lead in Children. A nationally-representative cross-sectional survey of children aged 1-4 years inclusive was done. Mean haematocrit and the proportion with anaemia using both the US and WHO haematocrit-based criteria were calculated. Multivariate regression was used to identify factors associated with haematocrit. Mean haematocrit level was 38.8% (95% CI: 38.6 - 39.1%) and varied with age of child, state/territory of residence and whether the child was taking supplements. It did not vary by sex, Aboriginal identification, maternal birthplace, whether the child ate meat or any other selected characteristic. The factors identified explained only 4% of the variation in haematocrit levels. The prevalence of anaemia was 3.3% (95% CI: 2.4 - 4.5%) based on the US criteria and 2.0% (95% CI: 1.3 - 3.1%) based on the WHO criteria. The prevalence of anaemia in this national survey was lower than the prevalence of iron deficiency anaemia reported in several more localised studies.


Protective Effects of Green Tea Extract against Hepatic Tissue Injury in Streptozotocin-Induced Diabetic Rats.
Although diabetic hepatopathy is potentially less common, it may be appropriate for addition to the list of target organ conditions related to diabetes. This study was designed to evaluate the hepatoprotective properties of green tea extract (GTE) in STZ-induced diabetes in rats. Wistar rats were made diabetic through single injection of STZ (75 mg/kg i.p.). The rats were randomly divided into four groups of 10 animals each: Group 1, healthy control; Group 2, nondiabetics treated with GTE administered orally (1.5%, w/v); Group 3, diabetics; Group 4, diabetics treated with GTE (1.5%, w/v) for 8 weeks. Serum biomarkers were assessed to determine hepatic injury. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were measured to assess free radical activity in the liver tissue. Hepatic antioxidant activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were also determined. The biochemical findings were matched with histopathological verifications. Liver MDA content and serum levels of ALT, AST, ALP, and bilirubin in Group 3 significantly increased compared to Group 1 (P < 0.05) and significantly decreased in Group 4 compared to Group 3 (P < 0.05). Serum albumin level and GSH, SOD, CAT, and GSH-Px contents of the liver in Group 3 were significantly decreased compared to Group 1 (P < 0.05) and were significantly increased in Group 4 compared to Group 3 (P < 0.05). Histopathologically, the changes were in the same direction with biochemical findings. This study proved the hepatoprotective activity of GTE in experimentally induced diabetic rats.


The Emotional Foundations of Political Support: How Fear and Anger Affect Trust in the Government in Times of the Covid-19 Pandemic.
Crises like the current coronavirus pandemic evoke negative emotions in the general public. To date, however, little research has been conducted on the influence of these mental states on trust in the government - the uncontested key player in times of crises. Drawing on the appraisal and affective intelligence theories of emotions, we argue that fear and anger as the two crucial negative emotions in times of crises have divergent effects on trust in the government: Whereas fear leads to a rally-'round-the-flag effect increasing trust in the government, anger attributes blame for the adverse circumstances to the government. We present empirical evidence for our arguments with an original three-wave online panel survey of 1'600 Swiss residents during the unprecedented times of the coronavirus pandemic. Our analysis provides empirical support for our arguments and further shows that the relationship is strongest for right-wing respondents.


Immune checkpoint inhibitors as first-line therapy for non-small cell lung cancer: A systematic evaluation and meta-analysis.
Recently, immune checkpoint inhibitors (ICIs) present promising application prospects in treating non-small cell lung cancer (NSCLC). This study aimed to investigate optimal treatment strategy by comparing the first-line treatment strategies with ICIs in NSCLC. We retrieved relevant studies on first-line therapy of NSCLC with ICIs. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were treatment-related serious adverse events (tr-SAEs) with grade 3 or higher and objective response rate (ORR). We also conducted a Bayesian network meta-analysis. We included 14 studies involving 7,823 patients and compared seven different interventions. In PD-L1 nonselective NSCLC, nivolumab+ipilimumab had good PFS and ORR, pembrolizumab significantly prolonged OS, and nivolumab had the fewest adverse events (AEs). For PD-L1-positive patients, nivolumab remarkably prolonged OS. For those with negative PD-L1, nivolumab+ipilimumab also showed an advantage. In addition, nivolumab+ipilimumab significantly prolonged the PFS in both PD-L1-negative and -positive patients. For patients with PD-L1 tumor proportion score (TPS) within 1-49%, atezolizumab+chemotherapy remarkably prolonged PFS and OS. For those with PD-L1 TPS ≥50%, pembrolizumab prolonged OS and atezolizumab+chemotherapy significantly prolonged PFS. Nivolumab combined with ipilimumab showed advantages in OS, PFS and ORR in most patients. Nivolumab+ipilimumab may be the optimal first-line therapy for NSCLC.


The Production of Niacin by Microorganisms Isolated from Fermenting Corn Meal 1.
Twenty-eight microorganisms, which were isolated from a natural fermentation of corn meal, were screened for niacin production in Difco niacin assay medium. Bacillus licheniformis strains 6, 9, and 10 grew in the synthetic medium free from niacin, indicating that these strains are indeed able to synthesize niacin. The amount of niacin was assayed according to a microbiological assay procedure using Lactobacillus plantarum ATCC 8014 as the assay organism. The three strains of B. licheniformis produced almost the same amount of niacin. When corn meal was fermented with pure cultures of B. licheniformis strains 9 and 10, the niacin content significantly (p<0.05) increased as compared to the nonfermented corn meal. Strain 10 produced the largest quantity of niacin in fermented corn meal at pH 7 and 35°C.


Optical imaging in microfluidic bioreactors enables oxygen monitoring for continuous cell culture.
For the first time, a fluorescence lifetime calibration method for an oxygen-sensitive dye ruthenium tris(2,2'-dipyridyl) dichloride hexahydrate (RTDP) is applied to image oxygen levels in poly(dimethyl siloxane) (PDMS) bioreactors containing living C2C12 mouse myoblasts. PDMS microsystems are broadly used in bioengineering applications due to their biocompatibility and ease of handling. For these systems, oxygen concentrations are of significance and are likely to play an important role in cell behavior and gene expression. Fluorescence lifetime imaging microscopy (FLIM) bases image contrast on fluorophore excited state lifetimes, which reflect local biochemistry. Unique attributes of the widefield, time-domain FLIM system include tunable excitation (337.1 to 960 nm), large temporal dynamic range (> or =600 ps), high spatial resolution (1.4 microm), calibrated detection (0 to 300+/-8 microM of oxygen), and rapid data acquisition and processing times (10 s). Oxygen levels decrease with increasing cell densities and are consistent with model outcomes obtained by simulating bioreactor oxygen diffusion and cell proliferation. In single bioreactor loops, FLIM detects spatial heterogeneity in oxygen levels with variations as high as 20%. The fluorescence lifetime-based imaging approach we describe avoids intensity-based artifacts (including photobleaching and concentration variations) and provides a technique with high spatial discrimination for oxygen monitoring in continuous cell culture systems.


Demonstration of anatomical development of the human macula within the first 5 years of life using handheld OCT.
To demonstrate the anatomical development of the human macula using handheld spectral domain optical coherence tomography (SD-OCT) during the first 5 years of life. This study is a cross-sectional, observational case series. Thirty-five normal eyes of 35 full-term/late preterm infants and children under 5 years of age were included. Handheld SD-OCT was used to image the macula of each eye. The data were analyzed using the Duke OCT Retinal Analysis Program v17 software. Retinal thickness maps were generated for the total retinal thickness (TRT), the inner retinal layers thickness (IRL), and the photoreceptor layer thickness (PRL). Based on the early treatment diabetic retinopathy study macular map, average thickness measurements were taken at 4 circles centered on the fovea (diameter): the foveal center (0.5 mm), sector 1 (S1) (1 mm), sector 2 (S2) (3 mm), sector 3 (S3) (6 mm). The median age at participation was 24 months (range 5-52 months). The TRT increased throughout the first 5 years of life, and this increase was statistically significant at the foveal center and S1 (p = 0.01, p = 0.016, respectively). The IRL did not show any significant change in thickness from birth and throughout the first 5 years of life. The PRL thickness showed thickening in the first 24 months of age at the foveal center and S1 which was statistically significant at S1 (p = 0.066, p = 0.016, respectively). Interestingly, this PRL thickness increase plateaus beyond 24 months of age. The photoreceptors inner segment/outer segment (IS/OS) band was identified as a distinct layer in all our subjects. Our findings conform with the literature that the anatomical development of the macular IRL completes before 5 months of age and hence before the PRL. We also identify 24 months of age as an important developmental milestone for photoreceptors development in the human macula.


[Acute spinal epidural hematoma complicated with essential thrombocytosis].
An 82-year-old woman was brought to our hospital with back pain and paraplegia. Her platelet level was elevated to 456 x 10(4) x mm(-3). She was diagnosed as having acute spinal epidural hematoma complicated with essential thrombocytosis. After emergency decompression surgery, chemotherapy with hydroxycarbamide was performed and platelets decreased to 80 x 10(4) x mm(-3). There were no perioperative complications, such as hemorrhage or thrombosis in other organs.


Development and application of a processing model for the Irish dairy industry.
A processing-sector model was developed that simulates (i) milk collection, (ii) standardization, and (iii) product manufacture. The model estimates the product yield, net milk value, and component values of milk based on milk quantity, composition, product portfolio, and product values. Product specifications of cheese, butter, skim and whole milk powders, liquid milk, and casein are met through milk separation followed by reconstitution in appropriate proportions. Excess cream or skim milk are used in other product manufacture. Volume-related costs, including milk collection, standardization, and processing costs, and product-related costs, including processing costs per tonne, packaging, storage, distribution, and marketing, are quantified. Operating costs, incurred irrespective of milk received and processing activities, are included in the model on a fixed-rate basis. The net milk value is estimated as sale value less total costs. The component values of fat and protein were estimated from net milk value using the marginal rate of technical substitution. Two product portfolio scenarios were examined: scenario 1 was representative of the Irish product mix in 2000, in which 27, 39, 13, and 21% of the milk pool was processed into cheese (€ 3,291.33/t), butter (€ 2,766.33/t), whole milk powder (€ 2,453.33/t), and skim milk powder (€ 2,017.00/t), respectively, and scenario 2 was representative of the 2008 product mix, in which 43, 30, 14, and 13% was processed into cheese, butter, whole milk powder, and skim milk powder, respectively, and sold at the same market prices. Within both scenarios 3 milk compositions were considered, which were representative of (i) typical Irish Holstein-Friesian, (ii) Jersey, and (iii) the New Zealand strain of Holstein-Friesian, each of which had differing milk constituents. The effect each milk composition had on product yield, processing costs, total revenue, component values of milk, and the net value of milk was examined. The value per liter of milk in scenario 1 was 24.8, 30.8, and 27.4 cents for Irish Holstein-Friesian, Jersey, and New Zealand strain of Holstein-Friesian milk, respectively. In scenario 2 the value per liter of milk was 26.1, 32.6, and 28.9 cents for Irish Holstein-Friesian, Jersey, and New Zealand strain of Holstein-Friesian milk, respectively.


Pathogenesis and management of Staphylococcus epidermidis 'plastic' foreign body infections.
Staphylococcus epidermidis infections on foreign bodies made of plastic are caused by special and complex mechanisms. The staphylococcal cells are able to adhere to and grow on polymer surfaces in vivo and in vitro. In the course of colonization they produce an extracellular substance ('slime') which eventually covers them. It is thought that the staphylococcal slime has several biological functions, including promoting adhesion and protection against both antibiotics and host defence mechanisms. In patients, the removal of a colonized device should be accompanied by the parenteral administration of highly effective antistaphylococcal drugs, such as vancomycin.


Estimates of the treated prevalence of bipolar disorders by mental health services in the general population: comparison of results from administrative and health survey data.
Informed provision of population mental health services requires accurate estimates of disease burden. We estimated the treated prevalence of bipolar disorders by mental health services in the Calgary Zone, a catchment area in Alberta with a population of over one million. Administrative data in a central repository provides information of mental health care contacts for about 95% of publically funded mental health services. We compared this treated prevalence against self-reported data in the 2002 Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2). Of the 63 016 individuals aged 18 years plus treated in the Calgary Zone in 2002-2008, 3659 (5.81%) and 1065 (1.70%) were diagnosed with bipolar I and bipolar II disorder, respectively. The estimated treated population prevalence of these disorders was 0.41% and 0.12%, respectively. We estimated that 0.44% to 1.17% of the Canadian population was being treated by psychiatrists for bipolar I disorder from CCHS 1.2. For bipolar I disorder the estimate based on local administrative data is close to the lower end of the health survey range. The degree of agreement in our estimates reinforces the utility of administrative data repositories in the surveillance of chronic mental disorders.


Successful increase in contraceptive uptake among Kenyan HIV-1-serodiscordant couples enrolled in an HIV-1 prevention trial.
To evaluate a multipronged approach to promote dual contraceptive use by women within heterosexual HIV-1-serodiscordant partnerships. For 213 HIV-1-serodiscordant couples in Thika, Kenya, participating in an HIV-1 prevention clinical trial, contraceptive promotion was initiated through a multipronged intervention that included staff training, couples family planning sessions, and free provision of hormonal contraception on-site. Contraceptive use and pregnancy incidence were compared between two time periods (before versus after June 2007, when the intervention was initiated) and between Thika and other Kenyan trial sites (Eldoret, Kisumu, and Nairobi). Generalized estimating equations and Andersen-Gill proportional hazards modeling were used. Nonbarrier contraceptive use increased after implementation of the intervention: from 31.5 to 64.7% of visits among HIV-1-seropositive women [odds ratio 4.0, 95% confidence interval (CI) 3.0-5.3] and from 28.6 to 46.7% of visits among HIV-1-seronegative women (odds ratio 2.2, 95% CI 1.4-3.5). In comparison, at the other Kenyan sites, where the intervention was not implemented, contraceptive use changed minimally, from 15.6 to 22.3% of visits for HIV-1-seropositive women and from 13.6 to 12.7% among HIV-1-seronegative women. Self-reported condom use remained high during follow-up. Pregnancy incidence at the Thika was significantly lower after compared with before June 2007 (hazard ratio 0.2, 95% CI 0.1-0.6) and was approximately half that at other Kenyan sites during the intervention period (hazard ratio 0.5, 95% CI 0.3-0.8). A multipronged family planning intervention can lead to high nonbarrier contraceptive uptake and reduced pregnancy incidence among women in HIV-1-serodiscordant partnerships.


Influence of methyldopa and bromocriptine on negative pressure breathing-induced diuresis.
The effects of methyldopa, a central alpha 2-agonist, and bromocriptine, a dopaminergic drug, on negative pressure breathing-induced diuresis were studied in the dog. Methyldopa (20 mg/kg i.v. during 20 min) or bromocriptine (0.3 mg/kg i.v.) suppressed the diuretic reflex without changing blood pressure. Since negative pressure breathing-induced diuresis is mainly due to an inhibition of vasopressin secretion, it is suggested that central alpha 2-adrenoceptors and dopaminergic receptors play an inhibitory role in mediating vasopressin release to non osmotic stimuli.


Surgical excision of duodenal/pancreatic metastatic renal cell carcinoma.
Renal cell carcinoma (RCC) has a potential to metastasize to almost any site and this may occur many years following nephrectomy. We present six cases with uncommon sites of metastasis: four patients presented with distal pancreatic metastasis and two with duodenal/head of the pancreas metastasis. Time to metastatic disease varied from 1 to 19 years following renal surgery. For patients are alive and two succumbed to their disease. Long-term survival can be achieved with aggressive surgical excision of disease.


NB1, a new neutrophil-specific antigen involved in the pathogenesis of neonatal neutropenia.
A new human antigen is reported which is present only on blood neutrophils. A neutrophil-specific antigen, designated NA1, has previously been identified in two unrelated families, and was shown to be involved in fetomaternal incompatibility and the development of isoimmune neonatal neutropenia in five newborns. In the present paper, a second antigen, designated NB1, is identified in four families with seven affected children. Antibodies that react with this second antigen are shown to produce selective agglutination of neutrophils but not other blood cells. They are neither absorbed by cells prepared from solid tissues nor by non-neutrophilic blood cells. By family and population studies, NB is shown to be distinct from NA, representing an independent genetic locus. 68% of the New York population are homozygous for NB1, 29% heterozygous, and 3% negative. The NB locus is shown to be independent from those of HL-A and other known leukocyte antigens. No evidence for linkage between NA, NB, and red cell antigens was obtained.


[Imaging of childhood brain tumors].
Brain tumors represent around a quarter of all solid tumors observed in the pediatric population. Infratentorial tumors are the most frequent, mostly encountered between 4 and 11 years of age. Early imaging is important because initial symptoms can be misinterpreted as statural and pubertal disorders or pseudoabdominal symptoms with apathy and vomiting in infants. Because signal abnormalities on MRI are most often not specific, it is essential to take into account the clinical and topographic characteristics of the lesion to establish an appropriate differential diagnosis. The main patterns of brain tumors observed in pediatrics are presented. Brain metastases are very unusual in children, in contrast to lepto-meningeal metastasis.


Comparison of Mesenchymal Stromal Cells From Different Origins for the Treatment of Graft-vs.-Host-Disease in a Humanized Mouse Model.
Mesenchymal stromal cells (MSCs) have potent immunomodulatory properties that make them an attractive tool against graft- vs.-host disease (GVHD). However, despite promising results in phase I/II studies, bone marrow (BM-) derived MSCs failed to demonstrate their superiority over placebo in the sole phase III trial reported thus far. MSCs from different tissue origins display different characteristics, but their therapeutic benefits have never been directly compared in GVHD. Here, we compared the impact of BM-, umbilical cord (UC-), and adipose-tissue (AT-) derived MSCs on T-cell function in vitro and assessed their efficacy for the treatment of GVHD induced by injection of human peripheral blood mononuclear cells in NOD-scid IL-2Rγnull HLA-A2/HHD mice. In vitro, resting BM- and AT-MSCs were more potent than UC-MSCs to inhibit lymphocyte proliferation, whereas UC- and AT-MSCs induced a higher regulatory T-cell (CD4+CD25+FoxP3+)/T helper 17 ratio. Interestingly, AT-MSCs and UC-MSCs activated the coagulation pathway at a higher level than BM-MSCs. In vivo, AT-MSC infusions were complicated by sudden death in 4 of 16 animals, precluding an analysis of their efficacy. Intravenous MSC infusions (UC- or BM- combined) failed to significantly increase overall survival (OS) in an analysis combining data from 80 mice (hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.32-1.08, P = 0.087). In a sensitivity analysis we also compared OS in control vs. each MSC group separately. The results for the BM-MSC vs. control comparison was HR = 0.63 (95% CI 0.30-1.34, P = 0.24) while the figures for the UC-MSC vs. control comparison was HR = 0.56 (95% CI 0.28-1.10, P = 0.09). Altogether, these results suggest that MSCs from various origins have different effects on immune cells in vitro and in vivo. However, none significantly prevented death from GVHD. Finally, our data suggest that the safety profile of AT-MSC and UC-MSC need to be closely monitored given their pro-coagulant activities in vitro.


Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution: Implementation of Causal Inference Methods.
This report provides a final summary of the principal findings and key conclusions of a study supported by an HEI grant aimed at "Assessing Adverse Health Effects of Long-Term Exposure to Low Levels of Ambient Air Pollution." It is the second and final report on this topic. The study was designed to advance four critical areas of inquiry and methods development. First, it focused on predicting short- and long-term exposures to ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) at high spatial resolution (1 km × 1 km) for the continental United States over the period 2000-2016 and linking these predictions to health data. Second, it developed new causal inference methods for estimating exposure-response (ER) curves (ERCs) and adjusting for measured confounders. Third, it applied these methods to claims data from Medicare and Medicaid beneficiaries to estimate health effects associated with short- and long-term exposure to low levels of ambient air pollution. Finally, it developed pipelines for reproducible research, including approaches for data sharing, record linkage, and statistical software. Our HEI-funded work has supported an extensive portfolio of analyses and the development of statistical methods that can be used to robustly understand the health effects of short- and long-term exposure to low levels of ambient air pollution. Our Phase 1 report (Dominici et al. 2019) provided a high-level overview of our statistical methods, data analysis, and key findings, grouped into the following five areas: (1) exposure prediction, (2) epidemiological studies of ambient exposures to air pollution at low levels, (3) sensitivity analysis, (4) methodological contributions in causal inference, and (5) an open access research data platform. The current, final report includes a comprehensive overview of the entire research project. Considering our (1) massive study population, (2) numerous sensitivity analyses, and (3) transparent assessment of covariate balance indicating the quality of causal inference for simulating randomized experiments, we conclude that conditionally on the required assumptions for causal inference, our results collectively indicate that long-term PM2.5 exposure is likely to be causally related to mortality. This conclusion assumes that the causal inference assumptions hold and, more specifically, that we accounted adequately for confounding bias. We explored various modeling approaches, conducted extensive sensitivity analyses, and found that our results were robust across approaches and models. This work relied on publicly available data, and we have provided code that allows for reproducibility of our analyses. Our work provides comprehensive evidence of associations between exposures to PM2.5, NO2, and O3 and various health outcomes. In the current report, we report more specific results on the causal link between long-term exposure to PM2.5 and mortality, even at PM2.5 levels below or equal to 12 μg/m3, and mortality among Medicare beneficiaries (ages 65 and older). This work relies on newly developed causal inference methods for continuous exposure. For the period 2000-2016, we found that all statistical approaches led to consistent results: a 10-μg/m3 decrease in PM2.5 led to a statistically significant decrease in mortality rate ranging between 6% and 7% (= 1 - 1/hazard ratio [HR]) (HR estimates 1.06 [95% CI, 1.05 to 1.08] to 1.08 [95% CI, 1.07 to 1.09]). The estimated HRs were larger when studying the cohort of Medicare beneficiaries that were always exposed to PM2.5 levels lower than 12 μg/m3 (1.23 [95% CI, 1.18 to 1.28] to 1.37 [95% CI, 1.34 to 1.40]). Comparing the results from multiple and single pollutant models, we found that adjusting for the other two pollutants slightly attenuated the causal effects of PM2.5 and slightly elevated the causal effects of NO2 exposure on all-cause mortality. The results for O3 remained almost unchanged. We found evidence of a harmful causal relationship between mortality and long-term PM2.5 exposures adjusted for NO2 and O3 across the range of annual averages between 2.77 and 17.16 μg/m3 (included >98% of observations) in the entire cohort of Medicare beneficiaries across the continental United States from 2000 to 2016. Our results are consistent with recent epidemiological studies reporting a strong association between long-term exposure to PM2.5 and adverse health outcomes at low exposure levels. Importantly, the curve was almost linear at exposure levels lower than the current national standards, indicating aggravated harmful effects at exposure levels even below these standards. There is, in general, a harmful causal impact of long-term NO2 exposures to mortality adjusted for PM2.5 and O3 across the range of annual averages between 3.4 and 80 ppb (included >98% of observations). Yet within low levels (annual mean ≤53 ppb) below the current national standards, the causal impacts of NO2 exposures on all-cause mortality are nonlinear with statistical uncertainty. The ERCs of long-term O3 exposures on all-cause mortality adjusted for PM2.5 and NO2 are almost flat below 45 ppb, which shows no statistically significant effect. Yet we observed an increased hazard when the O3 exposures were higher than 45 ppb, and the HR was approximately 1.10 when comparing Medicare beneficiaries with annual mean O3 exposures of 50 ppb versus those with 30 ppb. institutions, including those that support the Health Effects Institute; therefore, it may not reflect the views or policies of these parties, and no endorsement by them should be inferred. A list of abbreviations and other terms appears at the end of this volume.


Historical and recent biological markers of exposure to fluoride.
Recent and historical biomarkers assess chronic or subchronic exposure to fluoride. The most studied recent biomarkers are nails and hair. Both can be non-invasively obtained, although collection of nails is more accepted by the subjects. External contamination may be a problem for both biomarkers and still needs to be better evaluated. Nails have been more extensively studied. Although the available knowledge does not allow their use as predictors of dental fluorosis by individual subjects, since reference values of fluoride have not yet been established, they have a strong potential for use in epidemiological surveys. Toenails should be preferred instead of fingernails, and variables that are known to affect nail fluoride concentrations - such as age, gender and geographical area - should be considered. The main historical biomarkers that could indicate total fluoride body burden are bone and dentin. Of these, bone is more studied, but its fluoride concentrations vary according to the type of bone and subjects' age and gender. They are also influenced by genetic background, renal function and remodeling rate, variables that complicate the establishment of a normal range of fluoride levels in bone that could indicate 'desirable' exposure to fluoride. The main issue when attempting to use bone as biomarker of fluoride exposure is the difficulty and invasiveness of sample collection. In this aspect, collection of dentin, especially from 3rd molars that are commonly extracted, is advantageous. However, mean values also span a wide range and reference concentrations have not been published yet.


Effect of calcium glycerophosphate on demineralization in an in vitro biofilm model.
The aim was to investigate the anti-caries properties of calcium glycerophosphate (CaGP) using an in vitro bacterial flow cell model. Four flow cells, inoculated from a chemostat containing a seven-organism bacterial consortium, were pulsed with sucrose twice daily, to provide an acidic challenge and pH-cycling conditions. Blocks of enamel and dentine were mounted in each flow cell. In a study on the effect of CaGP concentration, CaGP was pulsed into three of the flow cells, at the same time as the sucrose, to give concentrations of 0.10, 0.25 and 0.50%. Water was pulsed into the fourth flow cell with the sucrose. Microradiography revealed a significant dose response of decreasing demineralization as CaGP concentration increased. Reductions at 0.25 and 0.5% were significant when compared to the control. A second study investigated the effect of timing of CaGP pulsing, relative to sucrose, on enamel and dentine demineralization. CaGP (flow cell concentration 0.2%), was pulsed 1 h before, during or 1 h after the sucrose pulse; a water control was employed. In enamel, pulsing CaGP before the sucrose reduced demineralization significantly compared to concurrent pulsing, which in turn gave a significant reduction compared to pulsing after sucrose, which did not reduce demineralization significantly compared to the water control. In dentine, CaGP reduced demineralization significantly only when pulsed before the sucrose. The findings suggest that in vivo, the anti-caries potential of CaGP may be greater if it is applied before a cariogenic challenge.


Majority-Rules Effect and Allostery in Molecular Recognition of Calix[4]arene-Based Triple-Stranded Metallohelicates.
The triple-stranded metallohelicates 1 a,/1 b-3 a/3 b possessing internal guest binding cavities surrounded by calix[4]arene units were synthesized through coordination-driven self-assembly. UV/Vis titration experiments verified that the metallohelicates encapsulated N-methyl pyridinium cations bearing amino acid groups to form host-guest complexes. The guest chirality was transferred to the helicity of the helicates through the steric contact between the stereogenic center of the amino acid group and the metal cores. The (M) helicity was induced when guests the (R)-4--(R)-6 were accommodated within the cavities. The multiple guest complexation within the self-assembled helicates 2 a and 3 a displayed large positive cooperative effects, indicating that the first guest complexation preorganizes the rest of the cavities to facilitate a subsequent guest binding. This cooperativity results in the majority-rules effect in the chiral guest binding for 2 a and 3 a.


Insulin-like growth factor-I controls BRCA1 gene expression through activation of transcription factor Sp1.
The insulin-like growth factors (IGFs) have a central role in mammary gland growth and differentiation as well as in breast cancer development. The BRCA1 gene encodes a pleiotropic protein that functions as a transcription factor. Germline BRCA1 mutations are associated with inherited predisposition to breast and ovarian cancer and confer a substantially increased risk for developing these neoplasms. Several lines of evidence led us to hypothesize that there is a functional interaction between the BRCA1 and IGF-I systems relevant to breast cancer biology. The present study tested the notion that BRCA1 gene expression is regulated by the IGF-I signaling pathway. Results of Western immunoblotting and RT-PCR analyses show that IGF-I stimulates BRCA1 protein and mRNA levels. Transient transfection experiments using BRCA1 promoter-luciferase reporter constructs reveal that IGF-I enhances BRCA1 promoter activity, suggesting that the effect of IGF-I is mediated at the transcriptional level. In addition, we provide evidence that the Sp1 zinc-finger protein is directly involved in BRCA1 gene transactivation. Combined, our data suggests that, at least part of the biological actions of IGF-I in mammary gland cells may be mediated through BRCA1. Dysregulated BRCA1 expression resulting from aberrant IGF signaling may have important consequences relevant to breast cancer pathogenesis.


Evaluation and development of potentially better practices to improve the discharge process in the neonatal intensive care unit.
Our goal was to identify potentially better practices that create a successful discharge planning process that spans the entire newborn intensive care stay to the next level of care by embedding the discharge planning into all aspects of patient care and communication. Potentially better practices were developed through recommendations from a content expert and a literature review. Internal benchmarking, self-assessment tools, monthly conference calls, the Neonatal Intensive Care Quality Improvement Collaborative 2002 listserv, parent feedback, and semiannual conferences were used to finalize recommendations and implement practices. Potentially better practices included (1) create an easy-to-use/easy-to-access discharge planning tool kit, (2) restructure written and oral communication tools and processes to reflect plans for the day, the stay, and the way to discharge, (3) maximize the impact and use of caregiver educational tools, and update materials and delivery systems for caregiver education, (4) use continuous quality improvement tools and processes to ensure parent/caregiver and staff satisfaction, and (5) analyze and enhance transfers into and interactions with the community. The potentially better practices are recommendations that are designed to integrate organizational, clinical, and operational processes to ensure optimal discharge planning from admission through follow-up in the community.


Characterization of relevant bovine dander allergen components.
The diagnostics of allergic occupational diseases is highly dependent on the quality of the allergen extracts and specific IgE tests available. To enhance the diagnostics of bovine-related occupational rhinitis, asthma and urticaria, we produced an in-house cow dander extract, assessed its allergen profile and performance in clinical tests, and compared it to commercial bovine dander extracts. One hundred patients with a suspected bovine-related occupational disease underwent skin prick tests (SPTs) with in-house and one to two commercial bovine dander extracts. Nasal allergen provocation tests were performed on 31 patients with suspected occupational rhinitis. We used Western blot to study the specific IgE-protein reactions from the serums of the patients with positive provocation tests, and identified allergens from immunoblot bands using tandem mass spectrometry. Odorant-binding protein Bos d OBP, bovine serum albumin Bos d 6, and lipocalin Bos d 2 were identified as the major allergens. We found altogether 24 bovine dander allergens, of which several were formerly unknown. The in-house extract sensitivity and specificity in SPTs were 100% and 94%, in 87 patients respectively and SPTs appeared negative in 20 healthy controls. Nasal allergen provocation tests with inhouse extract detected occupational rhinitis with 100% sensitivity in 21 patients. Five healthy controls remained negative in the provocation tests. Three major and several minor allergens were found from bovine dander as a cause of occupational rhinitis. A sufficient concentration and variety of tested allergens were essential in the diagnostics of bovine-related occupational diseases.


Probing the local structure of pure ionic liquid salts with solid- and liquid-state NMR.
Room-temperature ionic liquids (RTILs) are gaining increasing interest and are considered part of the green chemistry paradigm due to their negligible vapour pressure and ease of recycling. Evidence of liquid-state order, observed by IR and Raman spectroscopy, diffraction studies, and simulated by ab initio methods, has been reported in the literature. Here, quadrupolar nuclei are used as NMR probes to extract information about the solid and possible residual order in the liquid state of RTILs. To this end, the anisotropic nature and field dependence of quadrupolar and chemical shift interactions are exploited. Relaxation time measurements and a search for residual second-order quadrupolar coupling were employed to investigate the molecular motions present in the liquid state and infer what kind of order is present. The results obtained indicate that on a timescale of approximately 10(-8) sec or longer, RTILs behave as isotropic liquids without residual order.


Numerical Simulation of the Impact of the Heat Source Position on Melting of a Nano-Enhanced Phase Change Material.
A 2D-symmetric numerical study of a new design of Nano-Enhanced Phase change material (NEPCM)-filled enclosure is presented in this paper. The enclosure is equipped with an inner tube allowing the circulation of the heat transfer fluid (HTF); n-Octadecane is chosen as phase change material (PCM). Comsol-Multiphysics commercial code was used to solve the governing equations. This study has been performed to examine the heat distribution and melting rate under the influence of the inner-tube position and the concentration of the nanoparticles dispersed in the PCM. The inner tube was located at three different vertical positions and the nanoparticle concentration was varied from 0 to 0.06. The results revealed that both heat transfer/melting rates are improved when the inner tube is located at the bottom region of the enclosure and by increasing the concentration of the nanoparticles. The addition of the nanoparticles enhances the heat transfer due to the considerable increase in conductivity. On the other hand, by placing the tube in the bottom area of the enclosure, the liquid PCM gets a wider space, allowing the intensification of the natural convection.


Clinical outcome following aleatory implantation of paclitaxel-eluting or sirolimus-eluting stents in complex coronary lesions.
We compared the clinical efficacy of paclitaxel-eluting stents (PESs) and sirolimus-eluting stents (SESs) in a contemporary cohort of patients who had complex lesions. We collected data on 9-month outcomes in 529 patients (281 in the PES group and 248 in the SES group) whose de novo lesions were treated with drug-eluting stents. The end point was per-patient in-hospital and follow-up major adverse cardiac events, which were defined as a composite of death, myocardial infarction, and target vessel revascularization, including target lesion revascularization. There were no in-hospital deaths or repeat revascularizations; however, 5.7% of the PES group and 2% of the SES group developed a myocardial infarction (p = 0.04). At a median follow-up of 10.6 months, the rate of major adverse cardiac events was similar between groups (18.1% vs 21%, adjusted hazard ratio 0.85, 95% confidence interval 0.57 to 1.25), without any difference in the occurrence of death or myocardial infarction. Diabetes and total stent length were independent predictors of major adverse cardiac events. Propensity analysis confirmed the similarity between devices (hazard ratio 0.87, 95% confidence interval 0.62 to 1.25). Most restenoses were focal and only 2 patients required surgical revascularization. In conclusion, implantation of drug-eluting stents in complex lesions was associated with favorable results and most patients remained free from surgical revascularization at follow-up. Overall, the 2 available stent platforms had similar performance characteristics.


Multisensory causal inference in the brain.
At any given moment, our brain processes multiple inputs from its different sensory modalities (vision, hearing, touch, etc.). In deciphering this array of sensory information, the brain has to solve two problems: (1) which of the inputs originate from the same object and should be integrated and (2) for the sensations originating from the same object, how best to integrate them. Recent behavioural studies suggest that the human brain solves these problems using optimal probabilistic inference, known as Bayesian causal inference. However, how and where the underlying computations are carried out in the brain have remained unknown. By combining neuroimaging-based decoding techniques and computational modelling of behavioural data, a new study now sheds light on how multisensory causal inference maps onto specific brain areas. The results suggest that the complexity of neural computations increases along the visual hierarchy and link specific components of the causal inference process with specific visual and parietal regions.


Stereoscopic 3D geometric distortions analyzed from the viewer's point of view.
Stereoscopic 3D (S3D) geometric distortions can be introduced by mismatches among image capture, display, and viewing configurations. In previous work of S3D geometric models, geometric distortions have been analyzed from a third-person perspective based on the binocular depth cue (i.e., binocular disparity). A third-person perspective is different from what the viewer sees since monocular depth cues (e.g., linear perspective, occlusion, and shadows) from different perspectives are different. However, depth perception in a 3D space involves both monocular and binocular depth cues. Geometric distortions that are solely predicted by the binocular depth cue cannot describe what a viewer really perceives. In this paper, we combine geometric models and retinal disparity models to analyze geometric distortions from the viewer's perspective where both monocular and binocular depth cues are considered. Results show that binocular and monocular depth-cue conflicts in a geometrically distorted S3D space. Moreover, user-initiated head translations averting from the optimal viewing position in conventional S3D displays can also introduce geometric distortions, which are inconsistent with our natural 3D viewing condition. The inconsistency of depth cues in a dynamic scene may be a source of visually induced motions sickness.


Regression of Hypervascular Nodules in a Patient with Wilson's Disease Awaiting Liver Transplantation.
This paper describes the regressive course over one year of hypervascular nodules in a patient with Wilson's disease. CT revealed multiple, enhancing nodules (up to 3 cm in diameter) detected in the liver in the early arterial phase after the administration of intravenous contrast material. Most of these nodules became isodense in the portal venous phase. After one year of efficient therapy combining d-penicillamine and zinc acetate, most of the nodules had disappeared, while the liver contours had become more regular. To our knowledge, the regression of large hypervascular nodules has not previously been reported in patients with Wilson's disease.


Quadrupedal gaits in hexapod animals - inter-leg coordination in free-walking adult stick insects.
The analysis of inter-leg coordination in insect walking is generally a study of six-legged locomotion. For decades, the stick insect Carausius morosus has been instrumental for unravelling the rules and mechanisms that control leg coordination in hexapeds. We analysed inter-leg coordination in C. morosus that freely walked on straight paths on plane surfaces with different slopes. Consecutive 1.7 s sections were assigned inter-leg coordination patterns (which we call gaits) based on footfall patterns. Regular gaits, i.e. wave, tetrapod or tripod gaits, occurred in different proportions depending on surface slopes. Tetrapod gaits were observed most frequently, wave gaits only occurred on 90 deg inclining slopes and tripod gaits occurred most often on 15 deg declining slopes, i.e. in 40% of the sections. Depending on the slope, 36-66% of the sections were assigned irregular gaits. Irregular gaits were mostly due to multiple stepping by the front legs, which is perhaps probing behaviour, not phase coupled to the middle legs' cycles. In irregular gaits, middle leg and hindleg coordination was regular, related to quadrupedal walk and wave gaits. Apparently, front legs uncouple from and couple to the walking system without compromising middle leg and hindleg coordination. In front leg amputees, the remaining legs were strictly coordinated. In hindleg and middle leg amputees, the front legs continued multiple stepping. The coordination of middle leg amputees was maladapted, with front legs and hindlegs performing multiple steps or ipsilateral legs being in simultaneous swing. Thus, afferent information from middle legs might be necessary for a regular hindleg stepping pattern.


Health technology assessment: A necessity in post-sanctions Iran while implementing the health transformation plan.
Iran's health system is in the serious need of reconstructing its infrastructures, a significant part of which is health technologies. An untapped market of 80 million people will be open to technologies of the world through Iran's entry to post-sanctions era. Health Technology Assessment projects date back to nearly eight years ago in Iran. However, given the current circumstances, its application for selecting technologies is needed more than ever.


Toxicity studies of (+)-usnic acid administered in feed to F344/N Nctr rats and B6C3F1/Nctr mice.
(+)-Usnic acid is a secondary metabolite of lichens belonging to the Usnea genus. Usnea lichens and purified usnic acids have been used historically in traditional herbal medicine as bactericidal and antimicrobial agents. (+)-Usnic acid exhibits membrane proton uncoupling activity, which not only forms the mechanistic basis of its bactericidal action, but also has provided a rationale for its use as a fat-burning, weight-loss agent. Purified (+)-usnic acid has been marketed in the United States for this purpose either alone or in combination with other chemical agents. Use of some of these fat-burning products that contain (+)-usnic acid has resulted in serious liver damage. This study investigated the potential toxicity of (+)-usnic acid in male and female F344/N Nctr rats and B6C3F1/Nctr mice that were exposed via feed for 3 months. F344/N Nctr rats were administered 0, 30, 60, 120, 360, or 720 ppm in feed, while B6C3F1/Nctr mice were administered 0, 15, 30, 60, 180, or 360 ppm in feed. (Abstract Abridged).


Invertebrate models for biomedical research, testing, and education.
Invertebrate animals have been used as medicinals for 4,000 years and have served as models for research and teaching since the late 1800s. Interest in invertebrate models has increased over the past several decades as the research community has responded to public concerns about the use of vertebrate animals in research. As a result, invertebrates are being evaluated and recognized as models for many diseases and conditions. Their use has led to discoveries in almost every area of biology and medicine--from embryonic development to aging processes. Species range from terrestrial invertebrates such as nematodes and insects to freshwater and marine life including planarians, crustaceans, molluscs, and many others. The most often used models are the fruit fly Drosophila melanogaster and the minuscule nematode Caenorhabditis elegans. Topics in this article are categorized by biologic system, process, or disease with discussion of associated invertebrate models. Sections on bioactive products discovered from invertebrates follow the models section, and the article concludes with uses of invertebrates in teaching. The models reviewed can serve as references for scientists, researchers, veterinarians, institutional animal care and use committees (IACUCs), and others interested in alternatives to vertebrate animals.


Juvenile Moyamoya and Craniosynostosis in a Child with Deletion 1p32p31: Expanding the Clinical Spectrum of 1p32p31 Deletion Syndrome and a Review of the Literature.
Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterised by the progressive occlusion of the internal carotid artery. Its aetiology is uncertain, but a genetic background seems likely, given the high MA familial rate. To investigate the aetiology of craniosynostosis and juvenile moyamoya in a 14-year-old male patient, we performed an array-comparative genomic hybridisation revealing a de novo interstitial deletion of 8.5 Mb in chromosome region 1p32p31. The deletion involved 34 protein coding genes, including NF1A, whose haploinsufficiency is indicated as being mainly responsible for the 1p32-p31 chromosome deletion syndrome phenotype (OMIM 613735). Our patient also has a deleted FOXD3 of the FOX gene family of transcription factors, which plays an important role in neural crest cell growth and differentiation. As the murine FOXD3-/- model shows craniofacial anomalies and abnormal common carotid artery morphology, it can be hypothesised that FOXD3 is involved in the pathogenesis of the craniofacial and vascular defects observed in our patient. In support of our assumption, we found in the literature another patient with a syndromic form of MA who had a deletion involving another FOX gene (FOXC1). In addition to describing the clinical history of our patient, we have reviewed all of the available literature concerning other patients with a 1p32p31 deletion, including cases from the Decipher database, and we have also reviewed the genetic disorders associated with MA, which is a useful guide for the diagnosis of syndromic form of MA.


Hepatico-jejuno-duodenoplasty for biliary stricture.
The authors present the results of their experience in the therapy of biliary strictures, using a jejunal loop interposed between the biliary tract and duodenum. This procedure allows extensive biliary discharge and aims to prevent the pathophysiologic disturbances of gastroduodenal functions, which result from Roux-en-Y anastomosis, and has the advantages of both Roux-en-Y and choledochoduodenostomy procedures. The authors report nine years positive experience with this technique. No gastroduodenal postoperative complaints are reported in their series, whereas an 8% incidence of duodenal ulcers is reported after Roux-en-Y anastomoses.


Prognostic significance of intracellular laminin and Her2/neu overexpression in non-small cell lung cancer.
This study was designed to test the hypothesis that Her2/neu expression, the level of intracellular laminin and Ki-67 index are of prognostic importance in patients with non-small cell lung cancer (NSCLC). The second aim of the study was to analyse the efficiency of post-operative radiotherapy in the group of patients treated at our hospital. Tumor tissue samples were obtained from 64 patients with primary NSCLC, who were operated on and post-operatively irradiated. Immunohistochemical analyses were performed on paraffin blocks of resected lung tissue. Survival of the patients was calculated on the basis of 5-year follow up. From among the analysed factors only the enhanced expression of intracellular laminin, histological grade 3, adenocarcinoma type of cancer and statistically important radiotherapy parameters influenced patient survival. The influence of Her2/neu expression on survival almost reached statistical significance. In multivariate Cox analyses only the level of the intracellular laminin, overexpression of Her2/neu and dose time ratio (DTR) were found to be the independent risk factors for patients survival. Enhanced expression of intracellular laminin, Her2/neu overexpression and interruptions during post-operative radiotherapy are detrimental for survival in patients with NSCLC.


Using bodily postures to reduce anxiety and improve interoception: A comparison between powerful and neutral poses.
Previous research has shown that anxiety syndromes are highly prevalent among university students. Effective treatments are needed to reduce the burden of anxiety in this population. Powerful postures have been found to impact affective states, as well as interoception (i.e. the ability to perceive inner bodily signals). However, no previous study has compared the effects of powerful- and neutral postures in regards to anxiety and interoceptive ability. The first part of the study measured the single-session effect of adopting powerful- vs. neutral postures on students' (n = 57) interoceptive ability and state anxiety. The second part of the study measured the effect of adopting powerful or neutral postures twice daily for two weeks, on individuals' interoceptive ability and trait anxiety. State anxiety decreased in both conditions whereas interoceptive accuracy only increased in the power posing condition after a single session. Interoceptive accuracy increased in both groups after two weeks of training. The study included no comparison to a condition where individuals adopted their natural (i.e. usual) bodily posture. Embodiment interventions that include elements of adopting an open or expansive bodily posture whilst maintaining a self-focus, can help to reduce state anxiety and improve interoceptive accuracy in student populations. Power posing does not seem to be superior to holding a neutral posture to improve interoceptive accuracy or anxiety. One reason therefore could be that both conditions include the manipulation of self-focus and a postural change that diverges from individuals' normal posture.


Why I like nocturnal dialysis.
As with most things in life, this form of treatment is not for everybody. In my opinion, it is an option that should be explored if it is available. I have come to the conclusion that the advantages of nocturnal hemodialysis outweigh any of the possible disadvantages that there is no decision to make. My quality of life is so much better that I cannot envision going back to standard treatments. This is something that each patient will have to decide for themselves. Nocturnal dialysis has changed my life. For the better, even better than the few years of transplant, for this I thank my doctors, nurses and everyone else who has helped me along the way.


Investigation of the role of oxidative stress in amiodarone-induced pulmonary toxicity in the hamster.
Associated with amiodarone (AM) therapy is pneumonitis, which may progress to life-threatening pulmonary fibrosis. Although the etiology of amiodarone-induced pulmonary toxicity (AIPT) is unknown, a role for direct toxicity by oxidative stress has been proposed. We have used a single intratracheal administration of AM (1.8 mg (2.64 mumol)) to male golden Syrian hamsters to investigate the role of oxidative stress in AIPT. The antioxidant capacity of the lung was assessed following AM administration by evaluating glutathione status and antioxidant enzyme activities. The efficacy of treatment with the antioxidant agents butylated hydroxyanisole, diallyl sulfide, and N-acetylcysteine, in attenuation of AM-induced pulmonary fibrosis was also investigated. AM significantly (p < 0.05) increased the ratio of oxidized to total lung glutathione both 30 min (control, 0.93 +/- 0.23%; AM, 2.06 +/- 0.26%) and 120 min (control, 0.90 +/- 0.21%; AM, 3.58 +/- 1.34%) post administration. AM also increased activities of glutathione reductase (by 89%) 3 days post administration, and glutathione peroxidase (by 110 and 45%, respectively) and total superoxide dismutase (by 58 and 35%, respectively) both 3 and 7 days post administration. However, treatment of hamsters with butylated hydroxyanisole (150 mg.kg-1.day-1 s.c.) or diallyl sulfide (200 mg.kg-1.day-1, p.o.) for 3 days prior to AM, or treatment with N-acetylcysteine (10 mg intratracheally) 10 min prior to AM had no effect on pulmonary fibrosis 21 days post treatment, as determined by lung wet weight and hydroxyproline content, and had inconsistent effects on histologically determined disease index.(ABSTRACT TRUNCATED AT 250 WORDS)


Intrinsic vasodilation protects Wistar Kyoto rats from progressive glomerulosclerosis after unilateral nephrectomy.
Genetically determined differences in functional and structural determinants that govern the development of progressive glomerulosclerosis (GS) were studied in aging sham-operated or unilaterally nephrectomized male rats of two strains. Wistar rats showed an increase of proteinuria and GS with age, which was enhanced by unilateral nephrectomy (UN). In contrast, intact and UN Wistar Kyoto rats did not show an increase of proteinuria with age and 7 months after UN, no GS was seen in these rats. Systemic blood pressure was comparable in both strains and was not affected by UN. Functional studies in a separate group of rats 1 month after UN showed an identical increase in glomerular filtration rate in both strains as compared with sham-operated controls. The Wistar rats did not show an effect of UN on renal plasma flow, and consequently, there was an increase in filtration fraction, in contrast to Wistar Kyoto rats, which showed an increase in renal plasma flow with an unchanged filtration fraction. Glomerular volume was increased in both strains at 1 month and 7 months after UN. Mesangial expansion was not observed at 1 month after UN in either strain, which indicates that this is not a decisive factor in the development of GS. These data indicate that the genetically determined susceptibility to the development of GS in these two rat strains may be related to the degree of vasoconstriction, whereas glomerular volume expansion per se does not lead to GS but can well be a consequence of hyperfiltration. These studies are concordant with previous studies that revealed the role of hemodynamics in the pathogenesis of GS irrespective of glomerular expansion.


[Pediatric adder bites].
Adder bites and their progression to severe envenomations are more frequent in children than in adults. To describe the clinical, biological, and therapeutic characteristics of children bitten by adders and to identify risk factors associated with severe envenomations corresponding to grades II and III of the Audebert et al. classification (Toxicon 1992). A retrospective study was conducted between 2001 and 2009 in the pediatric emergency department of a tertiary children's hospital. The data collected were: age and sex of children; day and time of admission; day, time, and circumstances of the accident; snake identification; bite location; envenomation severity based on the Audebert et al. classification; presence of fang marks; prehospital care; use of specific immunotherapy (Viperfav(®)), associated treatments; length of stay; orientation, progression, and any complications. Fifty-eight children were included (43 boys, 15 girls). The mean age was 7.8 ± 4.1 years (range, 1.8-15 years). Bites occurred more often between 12:00 pm and 6:00 pm (62%), and were most often located in the lower extremities (77%). The classification of envenomation was: 83% low grade (grade 0, absence of envenomation, fang marks present; grade I, minor envenomation) and 17% high grade (grades II and III, moderate and severe envenomations). All high-grade envenomations received specific immunotherapy (Viperfav(®) F(ab')(2) fragments against Vipera aspis, Vipera berus, and Vipera ammodytes). The mean time from bite to Viperfav(®) injection was 23 ± 11 h (range, 8-36 h). Being bitten on the upper extremities (p < 0.001), during the afternoon (p = 0.025), feeling an immediate violent pain (p = 0.037), and high initial glycemia (p = 0.016) were associated with a significant risk of progressing to high-grade envenomation. There was no significant correlation between age, gender, and upper extremity bite. In the final model of the multivariate statistical analysis, three factors remained associated with this risk: bite location in the upper extremities (relative risk [RR] = 60.5 [3.5-1040[; p = 0.005), immediate violent pain (RR = 21.5 [1.3-364.5[; p = 0.03), and female gender (RR = 17.5 [0.9-320.3[; p = 0.053). A certain number of criteria seem related with a more significant risk of progression to high-grade envenomation following an adder bite. These results need to be studied on a larger cohort of patients. Bites to the upper extremities should be handled with caution because of the association with more severe envenomation.


Use of non-invasive ventilation in general ward for the treatment of respiratory failure.
Non-invasive ventilation (NIV), the provision of ventilatory assistance without an artificial airway, has emerged as an important ventilatory modality over the last 20 years. Delivery of pressured air at a certain level through a nasal or oro-nasal mask improves oxygenation and reduces ventilatory muscle fatigue. The equipment consists of a ventilator (typically a CPAP or BiPAP machine) with tubing, headgear, nasal or facial mask, filter and humidifier (Figure 1). In this article, we will discuss the medical literatures that support the use of NIV safely and effectively on the general medical floor to treat respiratory failure secondary to acute exacerbation of chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF).


Assessment of bronchodilator response in various spirometric patterns.
Spirometry is a physiologic test that measures the volume of air an individual inhales or exhales and the rate at which the volume is changed as a function of time. Bronchodilator response, as a beneficial test for diagnosis of bronchial responsiveness is measured using the percent change from baseline and absolute changes in forced expiratory volume in 1 second and/or forced vital capacity. In this study we aimed to assess the increase in spirometric parameters in patients with symptoms of asthma regardless of spirometric pattern. In this cross-sectional study bronchodilator test was performed in individuals with dyspnea, cough or wheezing and the mean increase in various spirometric parameters was measured and compared among individuals with different spirometric patterns. Among all individuals 24.5% responded to bronchodilator. Forced expiratory volume in 1 second was the parameter with the most frequent response to bronchodilator. Patients with mixed pattern had the highest frequency of response to bronchodilator. Response to bronchodilator was more than 50% in most mid flow volumes. Some patients with symptoms of asthma may show restrictive or mixed pattern in spirometry which may respond to bronchodilator administration.


Autologous Bone Graft From the Ipsilateral Distal Femur in Tibial Condyle Fractures.
Fractures of the proximal tibia often require void filling to support articular fragments in combination with internal fixation. The most common techniques are iliac autograft, allograft, or synthetic bone graft substitutes.The distal femur and its large volume condyles are a source of cancellous bone graft within the surgical site of an open reduction and internal fixation procedure. We have used a minimally invasive technique to harvest bone graft from the distal femur, using a bone graft drill. We performed this investigation to determine whether our technique of using distal femoral autograft to fill bone voids when treating proximal tibial fractures with open reduction and internal fixation is effective and safe. We also sought to determine the degree to which the bone graft incorporates into the tibia during fracture healing, the degree to which the harvest site heals, and the degree of secondary joint line depression.In all 12 patients, the bone graft had sufficient volume to fill the subchondral void in the proximal tibia, all fractures had healed at follow-up, and fracture reduction was maintained in most cases. We found no pain at the harvest site during follow-up, and there were no signs of drill penetration in articular or cortical structures. Drill holes at the harvest site showed sparse amounts of newly formed bone on CT in most of its circumference in all patients.There were no pathological changes in the femoral condyles with relation to the bone grafting procedure, and 5 patients showed radiographic signs of osteoarthritis in one or more joint compartments of the knee. The results showed this technique to provide similar success as reported alternatives without major complications and we continue to use this technique of harvesting distal femoral autograft to supplement open reduction and internal fixation of selected proximal tibial fractures.


Complexity of Nurse Practitioners' Role in Facilitating a Dignified Death for Long-Term Care Home Residents during the COVID-19 Pandemic.
Due to the interplay of multiple complex and interrelated factors, long-term care (LTC) home residents are increasingly vulnerable to sustaining poor outcomes in crisis situations such as the COVID-19 pandemic. While death is considered an unavoidable end for LTC home residents, the importance of facilitating a good death is one of the primary goals of palliative and end-of-life care. Nurse practitioners (NPs) are well-situated to optimize the palliative and end-of-life care needs of LTC home residents. This study explores the role of NPs in facilitating a dignified death for LTC home residents while also facing increased pressures related to the COVID-19 pandemic. The current exploratory qualitative study employed a phenomenological approach. A purposive sample of 14 NPs working in LTC homes was recruited. Data were generated using semi-structured interviews and examined using thematic analysis. Three categories were derived: (a) advance care planning and goals of care discussions; (b) pain and symptom management at the end-of-life; and (c) care after death. The findings suggest that further implementation of the NP role in LTC homes in collaboration with LTC home team and external partners will promote a good death and optimize the experiences of residents and their care partners during the end-of-life journey.


Barbiturate influence upon organization of lateral geniculate receptive fields in cats.
Under different levels of Nembutal anesthesia the spatiotemporal characteristics of receptive fields of cells in the lateral geniculate nucleus were investigated. All units decreased their maintained activity and bursts of spikes occurred spontaneously after administration of the anesthetic. The excitatory domains of the receptive fields were also changed by shortening of the cell's sustained response and enhancement of the postinhibitory transient responses; the spatial extent of these domains being less affected. A qualitatively new excitatory tertiary" domain appeared in the receptive field surround with a latency of 170-300 ms. These effects together with enhancement of the spatiotemporal extent of inhibitory domains suggest that the suppressive action of barbiturate takes place beyond the retina.


Carvedilol Selectively Stimulates βArrestin2-Dependent SERCA2a Activity in Cardiomyocytes to Augment Contractility.
Heart failure (HF) carries the highest mortality in the western world and β-blockers [β-adrenergic receptor (AR) antagonists] are part of the cornerstone pharmacotherapy for post-myocardial infarction (MI) chronic HF. Cardiac β1AR-activated βarrestin2, a G protein-coupled receptor (GPCR) adapter protein, promotes Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a SUMO (small ubiquitin-like modifier)-ylation and activity, thereby directly increasing cardiac contractility. Given that certain β-blockers, such as carvedilol and metoprolol, can activate βarrestins and/or SERCA2a in the heart, we investigated the effects of these two agents on cardiac βarrestin2-dependent SERCA2a SUMOylation and activity. We found that carvedilol, but not metoprolol, acutely induces βarrestin2 interaction with SERCA2a in H9c2 cardiomyocytes and in neonatal rat ventricular myocytes (NRVMs), resulting in enhanced SERCA2a SUMOylation. However, this translates into enhanced SERCA2a activity only in the presence of the β2AR-selective inverse agonist ICI 118,551 (ICI), indicating an opposing effect of carvedilol-occupied β2AR subtype on carvedilol-occupied β1AR-stimulated, βarrestin2-dependent SERCA2a activation. In addition, the amplitude of fractional shortening of NRVMs, transfected to overexpress βarrestin2, is acutely enhanced by carvedilol, again in the presence of ICI only. In contrast, metoprolol was without effect on NRVMs' shortening amplitude irrespective of ICI co-treatment. Importantly, the pro-contractile effect of carvedilol was also observed in human induced pluripotent stem cell (hIPSC)-derived cardiac myocytes (CMs) overexpressing βarrestin2, and, in fact, it was present even without concomitant ICI treatment of human CMs. Metoprolol with or without concomitant ICI did not affect contractility of human CMs, either. In conclusion, carvedilol, but not metoprolol, stimulates βarrestin2-mediated SERCA2a SUMOylation and activity through the β1AR in cardiac myocytes, translating into direct positive inotropy. However, this unique βarrestin2-dependent pro-contractile effect of carvedilol may be opposed or masked by carvedilol-bound β2AR subtype signaling.


Using a Mobile Application for Real-Time Collection of Patient-Reported Outcomes in Hepatopancreatobiliary Surgery within an ERAS® Pathway.
Patient-reported outcomes (PROs) are essential for patient-centered health care. This pilot study implemented a mobile application customized to an hepatopancreatobiliary Enhanced Recovery After Surgery (ERAS®) program-a novel environment-for real-time collection of PROs, including ERAS® pathway compliance. Patients undergoing hepatectomy, distal pancreatectomy, or pancreaticoduodenectomy through the ERAS® program were prospectively enrolled over 10 months. The application provided education and questionnaires before surgery through 30 days postdischarge. Thresholds were set for initial adoption of the application (75%), PRO response rate (50%), and patient satisfaction (75%). Daily postdischarge health checks integrated customized responses to guide out-of-hospital care. Of 165 enrolled patients, 122 met inclusion criteria. Application adoption was 93 per cent (114/122) and in-hospital engagement remained high at 88 per cent (107/122). Patients completed 62 per cent of PRO on quality of life, postoperative pain, nausea, opioid consumption, and compliance to ERAS® pathway items, including ambulation and breathing exercises. During postcharge tracking, 12 patients reported that the application prevented a phone call to the hospital and three patients reported prevention of an emergency room visit. PRO collection through this mobile device created an integrated platform for comprehensive perioperative care, patient-initiated outcome tracking with automatic reporting, and real-time feedback for process change. Improving proactive outpatient management of complex patients through mobile technology could help restructure health-care delivery and improve resource utilization for all patients.


A black sheep in Eresus (Araneae: Eresidae): taxonomic notes on the ladybird spiders of Iran and Turkey, with a new species.
New taxonomic data are provided on the ladybird spider genus Eresus Walckenaer, 1805 in Turkey and Iran. Eresus adaleari Zamani Szűts, sp. n. is described as a new species, on the basis of a single male specimen collected in Semnan Province, northeastern Iran, and Eresus lavrosiae Mcheidze, 1997, previously known solely from the original description of the male holotype from Georgia, is re-described on the basis of one newly collected male specimen from Kars Province, eastern Turkey. Both of these species are generally dark-colored, which contrasts with the usual coloration of males of this genus. Finally, a few methods and suggestions that might accelerate and improve taxonomic procedures for studying this group are discussed.


Travel Vaccination Update.
As international travel increases, an update on the current guidance regarding travel vaccinations is important for healthcare providers. There have been recent changes to availability of certain vaccines that providers should familiarize themselves with. This article provides adult and pediatric-specific guidance for the most commonly required and requested travel vaccines, particularly the Japanese encephalitis vaccine, typhoid vaccines, and the yellow fever vaccine.


Spinocerebellar ataxia type 4 (SCA4): Initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration.
Spinocerebellar ataxia type 4 (SCA4), also known as 'hereditary ataxia with sensory neuropathy', represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases.


The Measurement of Love: Psychometric Properties and Preliminary Findings of the Short Love Scale (SLS-12) in a Polish Sample.
There has been a perceived need for the development of instruments to assess relationship quality and love. The aim of this study was to describe the psychometric properties of the Short Love Scale (SLS-12) and to compare different measurement models. Data were collected using the CAWI (Computer-Assisted Web Interview) in Poland in early 2022 (18-60 years old; n = 941) among individuals living in formal or informal monogamous relationships. Both exploratory (EFA) and confirmatory factor (CFA) analyses were performed on two different subsamples obtained through random splitting of the full datafile. There were 12 items considered, which form three dimensions in accordance with the theoretical basis. CFA analysis confirmed good psychometric properties of the three-factor SLS-12 model based on EFA solution: χ2(47) = 146.802 (p ˂ 0.001); χ2/df = 3.123; CFI = 0.981, TLI = 0.973, RMSEA = 0.067 (90% CI 0.055-0.080), GFI = 0.952, AGFI = 0.921. SLS-12 subindices varied according to gender and relationship status. Based on ROC curve method, it may be assumed that scores on the SLS-12 ranging from 12 to 44 indicate a poor relationship, scores ranging from 45 to 52 a moderately good relationship, and scores of 53 to 60 a very good relationship. Improving and increasing the range of measures of love available to researchers remains an important task in supporting the progress of this area of research. Further research should be conducted among people of all ages living in both formal and informal relationships using the Short Love Scale-12 outlined in this paper.


Strain-induced yielding in bubble clusters.
We study how shearing clusters of two or four bubbles induces bubble separation or topological rearrangement. The critical deformation at which this yielding occurs is measured as a function of shear rate, liquid composition, and liquid content in the cluster. We establish a geometrical yield criterion in the quasistatic case on the basis of these experimental data as well as simulations. In the dynamic regime, the deformation where the cluster yields increases with the strain rate, and we derive a scaling law describing this phenomenon based on the dynamical inertial rupture of the liquid meniscus linking the two bubbles. Our experiments show that the same scaling law applies to two- and four-bubble clusters.


[Effects of high concentration manganese on active oxygen production and antioxidant enzyme activities in cucumber leaves under different irradiations].
Effects of high concentration manganese on active oxygen production and antioxidant enzymes in cucumber leaves under natural irradiation and 1/2 natural irradiation were studied. High concentration manganese increased the H2O2 content and O2*- producing rate of cucumber leaves (Fig.1A, B) and caused lipid peroxidation (Fig.1C). Compare to natural irradiation, 1/2 natural irradiation significantly decreased active oxygen production and lipid peroxidation (Fig.1). CAT activities in cytosols and chloroplasts were inhibited by high concentration manganese (Fig.2B), and other antioxidant enzyme activities were enhanced by high concentration manganese (Fig.2A, C-F). Especially activities of APX, DHAR and GR in chloroplasts were greatly stimulated by high concentration manganese under natural irradiation compared to 1/2 irradiation, which may play important roles in scavenging active oxygen species. Antioxidant enzymes in mitochondria showed higher activities under high concentration manganese under natural irradiation, but the differences were not significant under 1/2 natural irradiation (Fig.2A, C-F).


Prevalence of chronic obstructive pulmonary disease among those with serious mental illness.
Individuals with serious mental illness have elevated smoking rates, and smoking is a significant risk factor for chronic obstructive pulmonary disease (COPD). The goal was to determine the prevalence of COPD among those with serious mental illness. The authors surveyed a random sample of 200 adults with serious mental illness with questions from the National Health and Nutrition Examination Study III that were previously used to estimate the national prevalence of COPD. They compared the prevalence of COPD in the sample to a randomly selected matched subset of national comparison subjects. The prevalence of COPD was 22.6%. Those with serious mental illness were significantly more likely to have chronic bronchitis (19.5% versus 6.1%) and emphysema (7.9% versus 1.5%) than the comparison subjects. The prevalence of COPD is significantly higher among those with serious mental illness than comparison subjects. Improved primary and secondary prevention is warranted.