Comparison of repeatability of non-invasive and invasive urodynamics.
We have developed a method for the non-invasive measurement of urinary bladder pressure, and we apply this method in a longitudinal study of changes in bladder contractility in response to prostatic enlargement. In each volunteer in this study, we measure the bladder pressure twice. In the present study we have used this data to compare the repeatability of the non-invasive method to that of pressure-flow studies in a comparable population of patients. Difference plots were made of non-invasive bladder pressure measurements in 457 volunteers and of pressure-flow studies in a comparable population of 397 male patients. To compare the repeatability of two different methods for clinical measurement, the standard deviation of differences between repeated measurements in one individual needs to be normalised. Often a normalisation by dividing by the mean is done. We show that that normalisation may lead to erroneous results. We have normalised the standard deviations by dividing by the difference between the 97.5th and 2.5th percentile of the mean of the two observations in each subject. Normalised repeatability of the non-invasive method was 0.15, that of the various parameters derived from the pressure-flow studies varied from 0.11 to 0.22. We conclude that the repeatability of the tested non-invasive urodynamic method is comparable to, or slightly better than, that of pressure-flow studies. We further conclude that normalising standard deviations of differences by dividing by the difference between the 97.5th and 2.5th percentile of the mean is a suitable method to compare the repeatability of different methods for clinical measurement.


Out of the shadows: Chronic pain in Canadian Armed Forces veterans - Proceedings of a workshop at the 2019 Forum of the Canadian Institute for Military and Veteran Health Research.
This commentary summarizes proceedings of a workshop on chronic pain in military personnel and veterans (released personnel) at the Annual Forum of the Canadian Institute for Military and Veteran Health Research in Gatineau and Ottawa on October 22, 2019. The extent and impact of chronic pain among Canadian Armed Forces (CAF) veterans and their families is significant and has been underappreciated, largely due to limited disclosure by serving and veteran military personnel, stemming from a fear of stigmatization. Living with pain is seen as a fact of life in military cultures, something to be endured and not discussed. Though progress is being made in reducing the stigma of mental illness, the discourse on chronic pain remains censored. This workshop's goal was to bring the discussion of chronic pain out of the shadows in the search for ways to help veterans and active service personnel living with chronic pain. Many points of view were brought forward at this first national Canadian multidisciplinary gathering of researchers, veterans with lived experience, clinicians, and policymakers. A CAF member described his lived experience with constant chronic pain. Clinicians described aspects of chronic pain in military personnel and veterans whom they treat in their clinics. Dr. Ramesh Zacharias described the new Chronic Pain Center of Excellence for Canadian Veterans that will be established with funding from Veterans Affairs Canada. Dr. Norman Buckley highlighted collaboration with the existing Chronic Pain Network funded by the Canadian Institute for Health Research. Audience members identified a diverse variety of issues.


An update of the general health status in the indigenous populations of Malaysia.
Health scenarios are constantly evolving, particularly in developing countries but little is known regarding the health status of indigenous groups in Malaysia. This study aims to elucidate the current health status in four indigenous populations in the country, who by and large been left out of mainstream healthcare developments. Participants were recruited from the Temuan, Jehai, Kensiu and Bidayuh indigenous groups throughout Peninsula Malaysia and Sarawak. Health parameters including body mass index (BMI), blood pressure, casual blood glucose and, total cholesterol levels were measured using established methods. Malondialdehyde (MDA) and ferric-reducing antioxidant power (FRAP) levels were measured to assess oxidative stress status. Blood films were screened for evidence of microbial or parasitic infections and leukocyte differential counting was performed. The Temuan and Bidayuh who are more urbanized, had significantly higher mean body weight, BMI, total cholesterol (p<0.05) and higher prevalence of obesity and hypercholesterolemia. Low cholesterol levels, elevated eosinophil counts and increased total IgE, indicative of immune responses to infection or allergy, were recorded in the rural Kensiu and Jehai. The Kensiu had higher levels of FRAP and lower levels of MDA, whereas the reverse was found in the Temuan. This suggests reduced oxidative stress in the Kensiu compared to the Temuan. Expected correlations between FRAP and MDA levels with age, were evident in Jehai. Our findings reflect a shifting health burden and an epidemiological transition, particularly in the Temuan and Bidayuh. These changes could be attributed to dietary habits, lifestyles and socio-economic factors brought about by urbanization.


Insulin-Mediated Signaling Facilitates Resistance to PDGFR Inhibition in Proneural hPDGFB-Driven Gliomas.
Despite abundant evidence implicating receptor tyrosine kinases (RTK), including the platelet-derived growth factor receptor (PDGFR), in the pathogenesis of glioblastoma (GBM), the clinical use of RTK inhibitors in this disease has been greatly compromised by the rapid emergence of therapeutic resistance. To study the resistance of proneural gliomas that are driven by a PDGFR-regulated pathway to targeted tyrosine kinase inhibitors, we utilized a mouse model of proneural glioma in which mice develop tumors that become resistant to PDGFR inhibition. We found that tumors resistant to PDGFR inhibition required the expression and activation of the insulin receptor (IR)/insulin growth-like factor receptor (IGF1R) for tumor cell proliferation and survival. Cotargeting IR/IGF1R and PDGFR decreased the emergence of resistant clones in vitro Our findings characterize a novel model of glioma recurrence that implicates the IR/IGF1R signaling axis in mediating the development of resistance to PDGFR inhibition and provide evidence that IR/IGF1R signaling is important in the recurrence of the proneural subtype of glioma in which PDGF/PDGFR is most commonly expressed at a high level. Mol Cancer Ther; 16(4); 705-16. ©2017 AACR.


Adding palm oil to the diet of sheep alters fatty acids profile on yogurt: Benefits to consumers.
The aim of this study was to modify the fatty acid profile of yogurt from sheep milk by the inclusion of different concentrations of palm oil into their diet. Thus, thirty-six sheep during lactation were separated in four groups with nine animals each, as described below: the group T0 (0%); the group T2 (inclusion of 2% of palm oil); the group T4 (inclusion of 4% of palm oil) and the group T6 (inclusion of 6% of palm oil). After 60 days of the supplementation, milk samples were collected and yogurt was produced, which was evaluated regarding the concentration of saturated fatty acids (SFA), monounsaturated fatty acids (MFA), and polyunsaturated fatty acids (PFA). A significant reduction (p<0.05) in most SFA and a significant increase (p<0.05) on MFA and PFA was observed in the yogurt of sheep supplemented with 4 and 6% of palm oil. Consequently, it is possible to conclude that palm oil supplementation exerts positive effects on yogurt, since it led to the reduction of undesirable fatty acids and increased fatty acids beneficial to human health.


Chromatic dispersion and PMD mitigation at 10 Gb/s using Viterbi equalization for DPSK and DQPSK modulation formats.
We explore the potential of chromatic dispersion and polarization-mode dispersion (PMD) mitigation using Viterbi equalization in 10 Gb/s nonreturn-to-zero differential phase-shift keying (NRZ-DPSK) and differential quadrature phase-shift keying (NRZ-DQPSK) systems. We show through Monte Carlo simulations that using Viterbi equalization improves the performance of NRZ-OOK, NRZ-DPSK and NRZ-DQPSK receivers. For NRZ-DQPSK receiver with a Viterbi equalizer, the chromatic dispersion tolerance is about 5000 ps/nm and the 1st order PMD tolerance is about 160 ps at 3 dB OSNR penalty.


Human Trafficking and Health: A Survey of Male and Female Survivors in England.
To investigate physical and mental health and experiences of violence among male and female trafficking survivors in a high-income country. Our data were derived from a cross-sectional survey of 150 men and women in England who were in contact with posttrafficking support services. Interviews took place over 18 months, from June 2013 to December 2014. Participants had been trafficked for sexual exploitation (29%), domestic servitude (29.3%), and labor exploitation (40.4%). Sixty-six percent of women reported forced sex during trafficking, including 95% of those trafficked for sexual exploitation and 54% of those trafficked for domestic servitude. Twenty-one percent of men and 24% of women reported ongoing injuries, and 8% of men and 23% of women reported diagnosed sexually transmitted infections. Finally, 78% of women and 40% of men reported high levels of depression, anxiety, or posttraumatic stress disorder symptoms. Psychological interventions to support the recovery of this highly vulnerable population are urgently needed.


Both comorbidity and worse performance status are associated with poorer overall survival after external beam radiotherapy for prostate cancer.
In this retrospective study, we evaluated the biochemical recurrence rate, metastatic disease progression, and prostate cancer-specific and overall survival in patients curatively treated with external beam radiotherapy (EBRT) for early prostate cancer (PC). We also examined the prognostic effect of comorbidity by Charlson Comorbidity Index (CCI) and overall performance status by Eastern Clinical Oncology Group (ECOG) score. A total of 665 men treated between 2008 and 2013 were enrolled from Tampere University Hospital, Finland. Prostate-specific antigen (PSA) tests and hospital records were used to determine the 5-year survival for each aforementioned endpoint using a Kaplan-Meyer estimate. To analyze the impact of the selected prognostic factor, we used a Cox regression model to calculate the corresponding hazard ratio (HR) and 95% confidence interval (CI). With a median follow-up-time of 7.12 years, the 5-year overall survival (OS) after EBRT was 88.9% [86.5 -91.3%], prostate cancer-specific survival (PCSS) was 97.9% [96.7 -99.1%], metastasis-free survival (MFS) 94.8% [93.0 -96.6%] and biochemical recurrence-free survival (BRFS) 88.7% [86.2 -91.2%]. Both CCI (HR = 1.38, [1.25-1.51]) and ECOG score (HR = 1.63, [1.29-2.05]) declined OS, as well as Gleason score and T score (P < 0.05). Gleason score and T grade also associated to worse PCSS, MFS and BRFS. CCI and ECOG score are useful tools in evaluating the overall life expectancy of the patient after EBRT for PC. T-stage and Gleason score remain still the major prognostic factors.


Drosophila melanogaster Models of Friedreich's Ataxia.
Friedreich's ataxia (FRDA) is a rare inherited recessive disorder affecting the central and peripheral nervous systems and other extraneural organs such as the heart and pancreas. This incapacitating condition usually manifests in childhood or adolescence, exhibits an irreversible progression that confines the patient to a wheelchair, and leads to early death. FRDA is caused by a reduced level of the nuclear-encoded mitochondrial protein frataxin due to an abnormal GAA triplet repeat expansion in the first intron of the human FXN gene. FXN is evolutionarily conserved, with orthologs in essentially all eukaryotes and some prokaryotes, leading to the development of experimental models of this disease in different organisms. These FRDA models have contributed substantially to our current knowledge of frataxin function and the pathogenesis of the disease, as well as to explorations of suitable treatments. Drosophila melanogaster, an organism that is easy to manipulate genetically, has also become important in FRDA research. This review describes the substantial contribution of Drosophila to FRDA research since the characterization of the fly frataxin ortholog more than 15 years ago. Fly models have provided a comprehensive characterization of the defects associated with frataxin deficiency and have revealed genetic modifiers of disease phenotypes. In addition, these models are now being used in the search for potential therapeutic compounds for the treatment of this severe and still incurable disease.


Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm.
Cardiac rhythm is extremely robust, generating 2 billion contraction cycles during the average human life span. Transcriptional control of cardiac rhythm is poorly understood. We found that removal of the transcription factor gene Tbx5 from the adult mouse caused primary spontaneous and sustained atrial fibrillation (AF). Atrial cardiomyocytes from the Tbx5-mutant mice exhibited action potential abnormalities, including spontaneous depolarizations, which were rescued by chelating free calcium. We identified a multitiered transcriptional network that linked seven previously defined AF risk loci: TBX5 directly activated PITX2, and TBX5 and PITX2 antagonistically regulated membrane effector genes Scn5a, Gja1, Ryr2, Dsp, and Atp2a2 In addition, reduced Tbx5 dose by adult-specific haploinsufficiency caused decreased target gene expression, myocardial automaticity, and AF inducibility, which were all rescued by Pitx2 haploinsufficiency in mice. These results defined a transcriptional architecture for atrial rhythm control organized as an incoherent feed-forward loop, driven by TBX5 and modulated by PITX2. TBX5/PITX2 interplay provides tight control of atrial rhythm effector gene expression, and perturbation of the co-regulated network caused AF susceptibility. This work provides a model for the molecular mechanisms underpinning the genetic implication of multiple AF genome-wide association studies loci and will contribute to future efforts to stratify patients for AF risk by genotype.


Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-alpha-dependent mechanism.
Toll-like receptors (TLRs) are known to play a key role in the innate immune system particularly in inflammatory response against invading pathogens. Recent reports strongly indicate that they play important roles in cancer cells. Prostate cancer represents one of the most common cancer for which no cure is available once metastatic and androgen refractory. Since TLR3 has been recently suggested as a possible therapeutic target in some cancer cell lines, we studied TLR3 expression and functionality in two human prostate cancer cell lines, LNCaP and PC3. We report that both cell lines express TLR3 and that the TLR3 agonist poly (I:C) activates mitogen-activated protein kinases and induces inhibition of proliferation as well as caspase-dependent apoptosis. By using pharmacological and genetic approaches, we demonstrate the involvement of TLR3 in poly (I:C)-induced effects. We also show that a novel interferon-independent pathway involving protein kinase C (PKC)-alpha activation, upstream of p38 and c-jun N-terminal kinase, is responsible for poly (I:C) pro-apoptotic effects on LNCaP cells. To our knowledge, this is the first report describing a role of PKC-alpha in poly (I:C)-mediated apoptosis. The comprehension of the mechanisms underlying TLR3-mediated apoptosis can contribute tools to develop new agonists useful for the treatment of prostate cancer.


Antimicrobial activity of ceftolozane-tazobactam tested against Enterobacteriaceae and Pseudomonas aeruginosa with various resistance patterns isolated in U.S. Hospitals (2011-2012).
Ceftolozane/tazobactam, a novel antimicrobial agent with activity against Pseudomonas aeruginosa (including drug-resistant strains) and other common Gram-negative pathogens (including most extended-spectrum-β-lactamase [ESBL]-producing Enterobacteriaceae strains), and comparator agents were susceptibility tested by a reference broth microdilution method against 7,071 Enterobacteriaceae and 1,971 P. aeruginosa isolates. Isolates were collected consecutively from patients in 32 medical centers across the United States during 2011 to 2012. Overall, 15.7% and 8.9% of P. aeruginosa isolates were classified as multidrug resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% of Enterobacteriaceae were classified as MDR and XDR. No pandrug-resistant (PDR) Enterobacteriaceae isolates and only one PDR P. aeruginosa isolate were detected. Ceftolozane/tazobactam was the most potent (MIC50/90, 0.5/2 μg/ml) agent tested against P. aeruginosa and demonstrated good activity against 310 MDR strains (MIC50/90, 2/8 μg/ml) and 175 XDR strains (MIC50/90, 4/16 μg/ml). Ceftolozane/tazobactam exhibited high overall activity (MIC50/90, 0.25/1 μg/ml) against Enterobacteriaceae and retained activity (MIC50/90, 4/>32 μg/ml) against many 601 MDR strains but not against the 86 XDR strains (MIC50, >32 μg/ml). Ceftolozane/tazobactam was highly potent (MIC50/90, 0.25/0.5 μg/ml) against 2,691 Escherichia coli isolates and retained good activity against most ESBL-phenotype E. coli isolates (MIC50/90, 0.5/4 μg/ml), but activity was low against ESBL-phenotype Klebsiella pneumoniae isolates (MIC50/90, 32/>32 μg/ml), explained by the high rate (39.8%) of meropenem coresistance observed in this species phenotype. In summary, ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporary Enterobacteriaceae and P. aeruginosa isolates collected in U.S. medical centers. Importantly, ceftolozane/tazobactam retained potency against many MDR and XDR strains.


Effects of Total Intravenous Anesthesia and Low- and High-Flow Anesthesia Implementation on Middle Ear Pressure.
The middle ear is an air-filled lacuna in the temporal bone. Inhaled anesthetic agents increase the pressure of this lacuna. Therefore, attention must be paid in choosing not only anesthetic agents but also anesthetic method. This study compared the effects of high-flow total intravenous anesthesia (TIVA) and low- and high-flow desflurane anesthesia on middle ear pressure. Randomized prospective double-blind study. In this retrospective double-blind study, 90 patients (20-65 years old) scheduled to undergo elective thyroidectomies were divided into three randomized anesthesia groups: high-flow desflurane (Group I), low-flow desflurane (Group II), and high-flow TIVA (propofol, remifentanil) (Group III). The hemodynamic and respiratory parameters and tympanometry were measured before induction (T1), 10 minutes after intubation (T2), 10 minutes before the end of the operation (T3), and 5 (T4), 10 (T5), 15 (T6), and 30 (T7) minutes after the operation. No statistically significant differences were found in the age, gender, weight, height, body mass index, surgery duration, and anesthetic duration (p > 0.05). There were no statistically significant differences at T1, T3, T4, T5, T6, and T7 (p > 0.007), but there was a significant difference at T2 (p < 0.001), with Groups II and III having lower pressure than Group I (p < 0.001). The high-flow desflurane group had higher postinduction middle ear pressure values. Therefore, low-flow anesthesia and TIVA can be used more safely in middle ear surgeries, provided that a well-equipped anesthetic device and appropriate monitoring conditions are available.


Asymmetric breast dose in coronary angiography.
The purpose of this study was to demonstrate asymmetric radiation dose distribution to the breasts in coronary angiography. Gafchromic XR-QA2 film was used as an area dosimeter to capture the asymmetric dose distribution to the breasts at various tissue depths in an anthropomorphic phantom. A selection of tube angulations were used under a controlled experiment and during a mock coronary angiography procedure. The Gafchromic XR-QA2 film was able to confirm the asymmetric distribution of radiation dose to the breast and provide a normalized breast dose value. The right breast received the majority of dose for most of the tube angulations in the controlled experiment. However the left breast received the most radiation dose during the mock procedure. Asymmetric dose distribution to the breasts is normally not observed if Monte Carlo based simulations are performed because individual breast dose calculations are not available. The application of a typical coronary angiogram determined in the experiment showed the normalized left breast dose is 0.16 mGy/ Gy.cm2 and the right breast dose is 0.08 mGy/ Gy.cm2.


A Multi-objective Physiological Control for Continuous Flow Left Ventricular Assist Devices: Comparison of Estimator versus Sensor-based Feedback.
Left Ventricular Assist Devices have been successfully used for the treatment of Congestive Heart failure in patients who are not eligible for heart transplantation. This paper describes the implementation and comparison of the performance of a pressure sensor-based feedback controller. The strategies were tested on a mock loop of the systemic circulation. The results show that the use of pressure sensors generated a more accurate response of the controller compared to the use of estimators.Clinical Relevance- The study describes the integration of a LVAD physiological controller to a dynamic wireless monitoring system.


PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1.
Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.


Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour.
To explore the activity of pazopanib in solitary fibrous tumour (SFT). In a preclinical study, we compared the activity of pazopanib, sorafenib, sunitinib, regorafenib, axitinib and bevacizumab in a dedifferentiated-SFT (DSFT) xenotransplanted into Severe Combined Immunodeficiency (SCID) mice. Antiangiogenics were administered at their reported optimal doses when mean tumour volume (TV) was 80 mm(3). Drug activity was assessed as TV inhibition percentage (TVI%). From May 2012, six consecutive patients with advanced SFT received pazopanib, on a national name-based programme. In one case sunitinib was administered after pazopanib failure. In the xenograft model, pazopanib showed the lowest antitumour activity (21%TVI), while regorafenib was the most active (95%TVI). Sorafenib, bevacizumab, sunitinib were markedly active (78/70/65%TVI). Axitinib was marginally active (51%TVI). In the retrospective case-series, three patients carried malignant-SFT (MSFT), three DSFT. Best Response Evaluation Criteria in Solid Tumour (RECIST) responses were: three stable disease (SD), all MSFT, three progressive disease (PD), all DSFT, corresponding to one partial response (PR), two SD, three PD by Choi criteria. Median-progression-free survival was 3 months (range 1-15). In one patient, sunitinib was started after pazopanib failure, with a response. In dedifferentiated-SFT xenograft pazopanib induced a marginal antitumour activity, while regorafenib appeared the most active and promising agent. When administered in patients, pazopanib showed a modest activity in terms of tumour growth stabilisation, observed only in non-dedifferentiated cases.


[Science and medical education in Brazil (1930-1950)].
This article discusses the role of science and its impact on the curricula of medical schools between 1930 and 1950, sketching out the web of interrelations built up around these institutions, and bringing to light the connection between the contents of the curricula and the prevailing social, political and economic context. The scientific concepts at the time influenced the development of university level institutions, and had particular significance in medical education. In this period, the political and economic ties with the USA were manifested by the Rockefeller Foundation, especially in the arena of education and health. As a concept and working method as well as an ideological category, science was an important factor in standardizing the curricula of Brazil's medical schools, especially as concerned basic research.


High-throughput sequencing of complete human mtDNA genomes from the Caucasus and West Asia: high diversity and demographic inferences.
To investigate the demographic history of human populations from the Caucasus and surrounding regions, we used high-throughput sequencing to generate 147 complete mtDNA genome sequences from random samples of individuals from three groups from the Caucasus (Armenians, Azeri and Georgians), and one group each from Iran and Turkey. Overall diversity is very high, with 144 different sequences that fall into 97 different haplogroups found among the 147 individuals. Bayesian skyline plots (BSPs) of population size change through time show a population expansion around 40-50 kya, followed by a constant population size, and then another expansion around 15-18 kya for the groups from the Caucasus and Iran. The BSP for Turkey differs the most from the others, with an increase from 35 to 50 kya followed by a prolonged period of constant population size, and no indication of a second period of growth. An approximate Bayesian computation approach was used to estimate divergence times between each pair of populations; the oldest divergence times were between Turkey and the other four groups from the South Caucasus and Iran (~400-600 generations), while the divergence time of the three Caucasus groups from each other was comparable to their divergence time from Iran (average of ~360 generations). These results illustrate the value of random sampling of complete mtDNA genome sequences that can be obtained with high-throughput sequencing platforms.


Management of a malpositioned central venous catheter in the accessory hemiazygos vein.
Malposition of a central venous catheter (CVC) in the accessory hemiazygos vein is an uncommon but potentially fatal complication; however, there is limited information regarding the preferred removal technique. We report a patient, a 57-year-old woman, who presented with overdose of her prescribed sedatives, who experienced this catheter complication after CVC insertion in the left internal jugular vein. The CVC was placed without resistance but routine postplacement chest X-ray showed abnormal coursing of the catheter close to the descending aorta. We used non-enhanced CT as an adjunct to safely identify the catheter position and assess for any bleeding during removal. CT images taken after retraction of the catheter tip by 10 cm showed no bleeding and we were able to remove the catheter safely. We recommend using CT as an adjunct to safely remove malpositioned catheters and reduce the risk of further complication.


A Framework for Content-based Retrieval of EEG with Applications to Neuroscience and Beyond.
This paper introduces a prototype framework for content-based EEG retrieval (CBER). Like content-based image retrieval, the proposed framework retrieves EEG segments similar to the query EEG segment in a large database. Such retrieval of EEG can be used to assist data mining of brain signals by allowing researchers to understand the association between brain patterns, responses, and the environment. Retrieval might also be used to enhance the accuracy of Brain Computer Interface (BCI) systems by providing related samples for training. We present key components of CBER and explain how to handle the distinctive characteristics of EEG. To demonstrate the feasibility of the framework, we implemented a simple EEG database of about 37,000 samples from more than 100 subjects. We ran two retrieval scenarios with a set of EEG features and evaluation metrics. The results of finding similar subjects clearly demonstrate the potential of CBER in many EEG applications.


Diet composition determines course of hyperphagia in developing Zucker obese rats.
Previous observations from this laboratory indicate that, during growth, the hyperphagia of the male genetically obese Zucker rat reaches a peak or "breakpoint" and then declines. To examine the effect of dietary macronutrient content on the course of hyperphagia, groups of male lean and obese rats were maintained from 5-28 weeks of age on powdered chow, or isocaloric diets (3.6 kcal/g) containing 72% of calories as corn oil, dextrose, or soy isolate protein (n = 5 lean and obese rats/diet). On chow, hyperphagia was maintained at a level of 7-8 g above lean control intake until a "breakpoint" was reached at 17 weeks, and obese intake declined to lean control level. On the fat diet, hyperphagia was increased to 10 g/day when a breakpoint was reached at 8 weeks. On the dextrose and protein diets, hyperphagia at a level of 3-4 g/day reached breakpoints at weeks 18 and 16, respectively. On all diets, the intakes of obese rats were precisely equal to the intakes of lean control rats by weeks 19-20. These data show that the magnitude and duration of hyperphagia in the developing obese rat are influenced by diet composition. Previously, we have proposed that the obese rat's hyperphagia arises from rapid adipocyte filling. Since high-fat diets facilitate adipocyte enlargement, the early "breakpoint" of hyperphagia seen with the high-fat diet may indicate that this feeding stimulation decreases as the fat cells of the obese rat approach maximal size.


Blocking Autophagy in Cancer-Associated Fibroblasts Supports Chemotherapy of Pancreatic Cancer Cells.
In this study we evaluated the interaction of pancreatic cancer cells, cancer-associated fibroblasts, and distinct drugs such as α-cyano-4-hydroxycinnamate, metformin, and gemcitabine. We observed that α-cyano-4-hydroxycinnamate as monotherapy or in combination with metformin could significantly induce collagen I deposition within the stromal reaction. Subsequently, we demonstrated that cancer-associated fibroblasts impaired the anti-proliferation efficacy of α-cyano-4-hydroxycinnamate, metformin and gemcitabine. Interestingly, inhibition of autophagy in these fibroblasts can augment the anti-proliferation effect of these chemotherapeutics in vitro and can reduce the tumor weight in a syngeneic pancreatic cancer model. These results suggest that inhibiting autophagy in cancer-associated fibroblasts may contribute to strategies targeting cancer.


Analysis of the genes expressed in Clonorchis sinensis adults using the expressed sequence tag approach.
Clonorchis sinensis is a biliary tract parasite, which infects over 30 million people in China, Korea and Southeast Asia through the ingestion of undercooked freshwater fish that harbour the infective metacercariae. The genes expressed in C. sinensis adults were identified in order to develop novel drugs, better diagnostics and vaccines for the parasite. The C. sinensis cDNA library was constructed and DNA sequencing was performed with 450 randomly selected clones. Four hundred and fifteen clones contained the amino-acid-encoding sequences. The functions of these genes could be assigned by DNA sequence homology. Basic Local Alignment Search Tool X analysis showed that 277 of the 415 clones were strongly matched ( P<10(-9)) to previously identified proteins, while the remaining 138 fell into the "no database match" category. Among the clones matching previously identified proteins, 220 putatively identified genes were sorted into seven functional categories. These included the genes associated with energy metabolism (38), gene expression/RNA metabolism (21), regulatory/signalling components (14), protein metabolism/sorting (98), the structure/cytoskeleton (29), membrane transporters (ten) and antigenic proteins (ten). The remaining 57 clones were not included in these categories. The dataset included the genes encoding the proteases, a lipid binding protein, the antigen proteins and the other genes of interest from a diagnostics, drug or vaccine development viewpoint. The present expressed sequence tag analysis proved to be an effective tool for examining gene expression and identified several important genes which increase and complement our knowledge of the biology of C. sinensis.


Theoretical study of steady-state temperature rise within the eye due to ultrasound insonation.
The soft tissue thermal index (TIS), as defined in the AIUM/NEMA Output Display Standard, may not be relevant with respect to eye exposure, primarily because of differences in actual vs. assumed acoustic and thermal properties. Therefore, a theoretical study of temperature rise within the eye due to ultrasound insonation was undertaken to compare the TIS with more exact calculations. At each plane in the direction of propagation, the focused ultrasound beam was modeled as a disc of uniform intensity. Each disc becomes a heat source, and integration over all discs provides the total temperature rise at any axial position. Calculations were done assuming the ultrasound beam intersects the lens of the eye as well as for the case in which the beam does not intersect the lens. Results were found for frequencies of 7.0 MHZ to 40 MHZ, transducer diameters of 0.2 cm to 1.0 cm, and focal lengths ranging from 0.2 cm to 3.0 cm. Perfusion was assumed negligible and thermal and acoustic parameters were taken from reported studies. For every case, the ratio of maximum temperature rise to the TIS (assuming constant output power) was calculated. For the lens case, the ratio varied from 7.35 to 0.8. For the no-lens case, the ratio varied from 4.1 to 0.4. These results indicate that the TIS is not adequate to represent the temperature rise occurring within the eye upon insonation.


Age-related longitudinal change in cardiac structure and function in adults at increased cardiovascular risk.
Heart failure (HF) incidence increases markedly with age. We examined age-associated longitudinal change in cardiac structure and function, and their prediction by age and cardiovascular disease (CVD) risk factors, in a community-based cohort aged ≥60 years at increased CVD risk but without HF. CVD risk factors were recorded in 3065 participants who underwent a baseline echocardiographic examination, of whom 2358 attended a follow-up examination 3.8 [median, inter-quartile range (IQR) 3.5, 4.2] years later. Median age was 71 (IQR 67, 76) years and 55% of participants were male. Age was associated with longitudinal increase in left ventricular (LV) mass index (LVMI); decrease in LV volumes; increase in LV ejection fraction; decrease in mitral annular systolic velocity; decrease in diastolic function (decreased mitral early diastolic annular velocity (e'); and increase in left atrial volume index, mitral peak early diastolic flow velocity (E)/e' ratio, and tricuspid regurgitant velocity (TRVmax ) in men and women, except for TRVmax in men). In multivariable analysis, longitudinal increase in LVMI was explained by CVD risk factors alone, whereas age, together with CVD risk factors, independently predicted longitudinal change in all other echocardiographic parameters. CVD risk factors were differentially associated with longitudinal change in different echocardiographic parameters. Whereas the increase in LVMI with age was explained by CVD risk factors alone, age, together with risk factors, independently predicted longitudinal change in all other echocardiographic parameters, providing evidence for age-specific mechanisms of change in cardiac structure and function as people age. Age-associated change in LVMI, LV volumes, and diastolic function resembled what might be expected for the evolution of HF with preserved ejection fraction. Given the differential association of different CVD risk factors with longitudinal change in different echocardiographic parameters, therapies aimed at attenuation of age-associated change in cardiac structure and function, and HF evolution, will likely need to address multiple CVD risk factors.


Highly expressed miR-182-5p can promote preeclampsia progression by degrading RND3 and inhibiting HTR-8/SVneo cell invasion.
The role of miR-182-5p in preeclampsia was studied, and its mechanism was also explored. Fifty patients with preeclampsia were assigned to the study group and 50 normal pregnant women to the control group. The age, weight, blood pressure, urinary protein, and weight of newborns were compared between the two groups. The placental tissues of the above-mentioned subjects were collected, and quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) assay was used to detect the expression of miR-182-5p. MiR-182-5p was overexpressed or knocked down using a cell transfection assay in HTR-8/SVneov cell, which is a kind of human chorionic trophoblast cell. Changes in cell migration and invasiveness before and after transfection were determined by wound healing test and transwell assay, respectively. Western blot was performed to analyze the change of RND3 protein level before and after transfection. The biological prediction of the relationship between miR-182-5p and RND3 was performed and a dual luciferase reporter gene experiment was designed to verify the results. Finally, a rescue experiment was conducted to investigate whether RND3 could affect the role of miRNA-182-5p in the capacity of cell migration and invasion. Preeclampsia patients had higher systolic blood pressure, diastolic blood pressure, and urinary protein than normal pregnant women, while neonatal weight decreased compared with normal pregnant women. MiRNA-182-5p was highly expressed in placental tissues of patients with preeclampsia. After miRNA-182-5p was overexpressed, the migration and invasion of HTR-8/SVneo cells were significantly attenuated, and the mRNA and protein levels of RND3 were markedly downregulated, and vice versa. The dual luciferase reporting assay confirmed that miRNA-182-5p could bind to 3'UTR of RND3. In addition, the results of rescue experiment showed that overexpressing miRNA-182-5p could markedly inhibit the migration and invasion of HTR-8/SVneo cells; however, when RND3 was simultaneously overexpressed, the inhibitory effect of miRNA-182-5p was partially reversed. The highly expressed miRNA-182-5p in patients with preeclampsia promoted the development of preeclampsia, the possible mechanism of which might be that the increased miRNA-182-5p expression could inhibit the migratory and invasive ability of trophoblast cells through targeted degrading RND3 protein.


Look for the nerves! MR neurography adds essential diagnostic value to routine MRI in pediatric practice: a pictorial overview.
This study aimed to assess the feasibility of magnetic resonance (MR) neurography in children, and the potential roles of diffusion-weighted imaging (DWI) and fiber-tracking (FT) techniques. Five pediatric patients (age range: 6-12 years) underwent magnetic resonance imaging (MRI) for various clinical indications: neurogenic bladder (case 1); persistent hand pain following minor trauma (case 2); progressive atrophy of the lower left extremity muscles (case 3); bilateral hip pain (case 4); and palpable left supraclavicular mass (case 5). All studies were performed using a 1.5-T Avanto MRI scanner (Siemens, Erlangen, Germany). The protocol included 3D T2-weighted STIR and SPACE imaging, T1-weighted fat-saturation post-gadolinium imaging and diffusion tensor imaging (DTI) with tractography. ADC (N×10(-3) mm(2)/s) and FA values were calculated from regions of interest (ROIs) centered on the nerves. Nerve-fiber tracks were calculated using a fourth-order Runge-Kutta algorithm (NeuroD software). MR neurography allowed satisfactory visualization of all neural structures, and FA and ADC measurements were feasible. The final diagnoses were Tarlov cysts, median-nerve compression, sciatic perineurioma, Charcot-Marie-Tooth disease and plexiform neurofibroma in a patient with NF-1. FA and ADC measurements are of little value because of the lack of normal reference values. Nerve-fiber tractography (FT) may be of value in the characterization of tumor pathology, and is also helpful in the planning of surgical treatments. MR neurography is feasible in pediatric patients. However, a considerable amount of work has yet to be done to establish its role in the clinical management of the wide range of peripheral nerve diseases.


Human beta cell mass and function in diabetes: Recent advances in knowledge and technologies to understand disease pathogenesis.
Plasma insulin levels are predominantly the product of the morphological mass of insulin producing beta cells in the pancreatic islets of Langerhans and the functional status of each of these beta cells. Thus, deficiency in either beta cell mass or function, or both, can lead to insufficient levels of insulin, resulting in hyperglycemia and diabetes. Nonetheless, the precise contribution of beta cell mass and function to the pathogenesis of diabetes as well as the underlying mechanisms are still unclear. In the past, this was largely due to the restricted number of technologies suitable for studying the scarcely accessible human beta cells. However, in recent years, a number of new platforms have been established to expand the available techniques and to facilitate deeper insight into the role of human beta cell mass and function as cause for diabetes and as potential treatment targets. This review discusses the current knowledge about contribution of human beta cell mass and function to different stages of type 1 and type 2 diabetes pathogenesis. Furthermore, it highlights standard and newly developed technological platforms for the study of human beta cell biology, which can be used to increase our understanding of beta cell mass and function in human glucose homeostasis. In contrast to early disease models, recent studies suggest that in type 1 and type 2 diabetes impairment of beta cell function is an early feature of disease pathogenesis while a substantial decrease in beta cell mass occurs more closely to clinical manifestation. This suggests that, in addition to beta cell mass replacement for late stage therapies, the development of novel strategies for protection and recovery of beta cell function could be most promising for successful diabetes treatment and prevention. The use of today's developing and wide range of technologies and platforms for the study of human beta cells will allow for a more detailed investigation of the underlying mechanisms and will facilitate development of treatment approaches to specifically target human beta cell mass and function.


Measuring working memory in the Spanish population: Validation of a multiple shortened complex span task.
Working memory plays a key role in cognition as it is a major predictor of a wide range of higher order abilities and behaviors typical to daily life. Shorter versions of the complex span tasks (CSTs) have been recently developed, allowing for the reduction of test administration time without affecting validity and reliability in the measurement of working memory capacity (WMC). However, these short versions have not been validated for the Spanish-speaking population. The present work aimed to validate an English version of the shortened CSTs into Spanish in a sample of 325 university students (40% female; mean age = 21.04; SD = 2.80). Cronbach's coefficient alpha was computed for each complex span task as an index of internal consistency. Validity evidence was evaluated by comparing participants' scores on the three shortened complex span tasks (operation span, symmetry span, and rotation span) with two measures of reasoning ability (Raven's Advanced Progressive Matrices and Number Series) and using confirmatory factor analysis. Results indicated that the short version of the Spanish complex span has satisfying qualities for assessing WMC in a sample of university students, which is an initial step toward providing a valid and standardized method for assessing WMC in the Peninsular Spanish-speaking population. (PsycINFO Database Record


Cholinergic drugs alter ciliary muscle response and receptor content.
Topical echothiophate administration to the cynomolgus monkey eye for 5-6.5 months produced marked subsensitivity of the accommodative response to pilocarpine and a 65% decrease in specific high affinity 3H-QNB binding sites (ostensibly indicating muscarinic receptors) in the ciliary muscle. The decrease in 3H-QNB binding sites was quantitatively similar in surgically untouched, totally iridectomized, and ciliary muscle disinserted eyes. Following a 5-month off treatment recovery period, 3H-QNB binding sites increased to more than twice the number in untreated control eyes. In echothiophate-treated eyes whose contralateral eyes had previously received atropine+echothiophate, 3H-QNB binding sites were three to six times more numerous than in other long-term echothiophate-treated eyes, and one to two times more numerous than in untreated controls. Topical pilocarpine administration for 1 day to 7 months reduced ciliary muscle 3H-QNB binding sites by approximately 25%. Alterations in muscarinic receptors during and following cholinergic drug therapy may in part explain the observed subsensitization and recovery of ciliary muscle physiological responses.


Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides.
Insulin-like growth factor I (IGF-I), a 70-amino acid basic polypeptide, plays a fundamental role in postnatal mammalian growth as a major mediator through which growth hormone exerts its biological effects. We have recently identified two human IGF-I cDNAs which predict distinct peptide precursors of 153 and 195 amino acids. In the present study, both cDNAs were used to isolate and characterize the human IGF-I gene from genomic libraries. The IGF-I gene extends over at least 45 kilobase pairs and contains five exons interrupted by four introns. The DNA sequence of exons 1 through 4 encodes the 195-amino acid precursor, while exons 1, 2, 3, and 5 code for the 153-residue peptide, confirming the hypothesis that at least two IGF-I mRNAs are generated by alternative RNA processing of the primary gene transcript. The structure of the IGF-I gene resembles that of its companion somatomedin, IGF-II, as judged by the analogous location of two introns and considerable nucleotide and amino acid sequence similarity, but appears more distantly related to other members of the insulin gene family. Restriction endonuclease polymorphisms in the IGF-I gene, which map near exon 5 as determined by Southern blot analysis, will be useful in defining the genetics of familial growth failure.


[Chagas' disease and ischemic stroke].
American trypanosomiasis, known as Chagas' disease (CD) is a major Public Health problem in South America. Chronic cardiomyopathy is the most common clinical form of CD. Chagasic cardiomyopathy affects about 30 % of CD patients, and its manifestations begin on average 10-40 years after the initial infection. Chagas' cardiomyopathy is characterized by congestive heart failure, sudden cardiac death, intraventricular conduction defects, arrhythmias and thromboembolism. The relationship between Chagas' cardiomyopathy and ischemic stroke was reviewed. Significant variables that predict ischemic stroke in chagasic patients have been identified: apical aneurysm, cardiac insufficiency and cardiac arrhythmia. Prevalence of apical aneurysm in CD stroke patients has been estimated in 37%. The diagnosis of CD may be established after stroke presentation in at least 40% of patients. Chagasic cardiomyopathy should be included in the differential diagnosis of the etiology of stroke, being a potential source of cardioembolic stroke.


[Descriptive study of drug use among adolescents in higher middle education in Monterrey, Nueva León, Mexico].
We aimed to establish the consumption profile of licit and illicit drugs, consumption patterns and strategies for coping and resisting alcohol, tobacco and other drugs among adolescents in higher middle education. This study was based on concepts developed by specialized authors and considered the subject's behavioral, psychological and normative characteristics. The non-probabilistic sample consisted of 325 adolescents. Results indicated that 67%, 65% and 7% of the adolescents, respectively, accepted they had already used alcohol, tobacco and marijuana at some time in their life and that 33%, 38% and 3%, respectively, had used these same substances over the last month; 65% consider most of their colleagues have used these substances; 56% had to reject an offer to consume alcohol, 64% tobacco and 51% marijuana over the last month. On the basis of these findings, we recommend the implementation of a prevention program aimed at supporting the adolescent's resources to resist pressure towards consumption.


The childhood sexual abuse among youth in three Asian cities: Taipei, Shanghai, and Hanoi.
The article describes the prevalence and risk factors of childhood sexual abuse (CSA) among youth in Hanoi, Shanghai, and Taipei. Data used in this study are from the Three-City Asian Study of Adolescents and Youth, 2006-2007. Descriptive analysis and logistic regression models were used. The self-reported lifetime prevalence of CSA was 5.2% in Taipei, 1.3% in Shanghai, and 0.5% in Hanoi. The overall prevalence was 2.2% for females and 1.7% for males. The average age of first CSA was 10.5 years. Household instability, migration before age 14, and low maternal warmth were found to be positively associated with CSA, whereas discussing problems with father and being close to mother were negatively associated with CSA, after adjusting for sociodemographic characteristics. Our findings suggested the importance of prevention programs for preteen aged children, public education to raise awareness, and further prospective studies to identify various risk markers for CSA in Asia.


Health Literacy and Medication Adherence Among Patients Treated in a Free Health Clinic: A Pilot Study.
A patient's health literacy is not routinely assessed during visits with a health care provider. Since low health literacy is a risk factor for poor health outcomes, assessing health literacy should be considered as part of the standard medical workup. To evaluate the health literacy levels and medication adherence of patients treated by pharmacists in both the general medicine and the chronic care clinics at an urban free health clinic. Eligible patients from the free health clinic completed the Rapid Estimate of Adult Literacy in Medicine (REALM), a health literacy measurement tool, during their clinic visit in 2011. Medication adherence was self-reported by the patients. A total of 100 patients participated (mean age = 48). The majority of participants were female (56%) and white (55%). Most (64%) of the patients scored at a high school reading level according to REALM. Only 21% of participants read at a seventh- to eighth-grade level. Overall medication adherence rate was 73%. Forgetting to take medication was the most popular reason given for nonadherence. Disease state and adherence were significantly related in patients with HIV/AIDS and hypertension. Patient's ethnicity was significantly associated with literacy levels (P < .05). Although patients' literacy levels were not significantly associated with self-reported adherence in this population, availability of a patient's baseline health literacy level as a part of the medical record may help clinicians to individualize their interaction based on the patient's health literacy level in order to achieve better health outcomes, including improved medication adherence, especially for underserved populations.


Anxiety and fear related to coronavirus disease 2019 assessment in the Spanish population: A cross-sectional study.
The coronavirus disease 2019 pandemic has affected millions of people worldwide, compromising the responsiveness of governments and states and thus generating anxiety and fear at the population level. To assess the level of anxiety and fear of coronavirus disease 2019 in a Spanish adult population group. A descriptive cross-sectional study, using the anxiety and fear of COVID-19 assessment scale (AMICO, for its acronym in Spanish). The sample was composed of 1038 subjects. Univariate and bivariate statistical analyses were performed, after analysis of normality in the data distribution. Categorical regression analyses were also executed. The total sample size was 1036 subjects, 56.3% was made up of females, with a mean age of 48.11 years (SD = 15.13). The mean score obtained on the AMICO scale was 5.54 points (SD = 1.83), with a score range between 1.22 and 10. Bivariate analysis only demonstrated statistically significant differences in the mean score of the scale and the variables: sex, marital status, work area and academic level. The executed categorical regression analysis revealed an R2 value of 0.75 and a significance of p = 0.00. The results obtained show that the Spanish population presents moderate anxiety levels to coronavirus disease 2019. Women, married, with primary and/or secondary education level, and working in the public transport, services and/or hospitality sectors are more likely to have high levels of fear and anxiety. These results could be used for therapeutic and preventive psychological interventions, and also to plan new research under sex perspective and observing the socio-economic environment.


Enzybiotics LYSSTAPH-S and LYSDERM-S as Potential Therapeutic Agents for Chronic MRSA Wound Infections.
Antibacterial antibiotic therapy has played an important role in the treatment of bacterial infections for almost a century. The increasing resistance of pathogenic bacteria to antibiotics leads to an attempt to use previously neglected antibacterial therapies. Here we provide information on the two recombinantly modified antistaphylococcal enzymes derived from lysostaphin (LYSSTAPH-S) and endolysin (LYSDERM-S) derived from kayvirus 812F1 whose target sites reside in the bacterial cell wall. LYSSTAPH-S showed a stable antimicrobial effect over 24-h testing, even in concentrations lower than 1 µg/mL across a wide variety of epidemiologically important sequence types (STs) of methicillin-resistant Staphylococcus aureus (MRSA), especially in the stationary phase of growth (status comparable to chronic infections). LYSDERM-S showed a less potent antimicrobial effect that lasted only a few hours at concentrations of 15 μg/mL and higher. Our data indicate that these antimicrobial enzymes could be of substantial help in the treatment of chronic MRSA wound infections.


A comparison of the efficacy of trastuzumab deruxtecan in advanced HER2-positive breast cancer: active brain metastasis versus progressive extracranial disease alone.
Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with brain metastasis (BM), a group historically with poor outcomes. The prevalence of BMs in patients commencing T-DXd is currently unknown. No direct comparisons have been made of the activity of T-DXd in patients with active BM versus those with extracranial progression alone. This real-world study explored the prevalence of BMs in patients commencing T-DXd, the efficacy of T-DXd in active BM versus extracranial progression alone and the safety of T-DXd. Patients with human epidermal growth factor receptor 2-positive advanced breast cancer treated with T-DXd between June 2021 and February 2023 at our specialist cancer hospital were identified and notes reviewed. Clinicopathological information, prior treatment, the presence or absence of central nervous system (CNS) disease, outcomes and treatment-emergent adverse events (TEAEs) were recorded. Twenty-nine female patients, with a median age of 52 years (interquartile range 44-62 years), were identified; the prevalence of BM was 41%. Median number of lines of prior therapy was 2 (range 2-6). At a median follow-up of 13.8 months, median progression-free survival (PFS) for the overall population was 13.9 months [95% confidence interval (CI) 12.4 months-not estimable (NE)], 16.1 months (95% CI 15.1 months-NE) for active BMs and 12.4 months (95% CI 8.3 months-NE) for progressive extracranial disease alone. The 12-month overall survival (OS) rate was 74% (95% CI 59% to 95%) in the overall population, and 83% (95% CI 58% to 100%) and 66% (95% CI 45% to 96%) for active BMs and extracranial disease only, respectively. Most common TEAEs were fatigue, alopecia, and constipation. In nine patients (31%, including two deaths), pneumonitis occurred. In this real-world population, we demonstrate T-DXd to be effective in patients with active BMs and those with progressive extracranial disease alone. PFS and OS were numerically longer in those with active BMs. These data demonstrate that patients with active BM treated with T-DXd have at least comparable outcomes to those with extracranial disease alone. The high rate of pneumonitis warrants further consideration.


The genetic basis of traits associated with the evolution of serpentine endemism in monkeyflowers.
The floras on chemically and physically challenging soils, such as gypsum, shale, and serpentine, are characterized by narrowly endemic species. The evolution of edaphic endemics may be facilitated or constrained by genetic correlations among traits contributing to adaptation and reproductive isolation across soil boundaries. The yellow monkeyflowers in the Mimulus guttatus species complex are an ideal system in which to examine these evolutionary patterns. To determine the genetic basis of adaptive and prezygotic isolating traits, we performed genetic mapping experiments with F2 hybrids derived from a cross between a serpentine endemic, M. nudatus, and its close relative M. guttatus. Few large effect and many small effect QTL contribute to interspecific divergence in life history, floral and leaf traits, and a history of directional selection contributed to trait divergence. Loci contributing to adaptive traits and prezygotic reproductive isolation overlap, and their allelic effects are largely in the direction of species divergence. These loci contain promising candidate genes regulating flowering time and plant organ size. Together our results suggest that genetic correlations among traits can facilitate the evolution of adaptation and speciation and may be a common feature of the genetic architecture of divergence between edaphic endemics and their widespread relatives.


Unconventional therapy in Pennsylvania practices.
The public's interest in "alternative" medicine is well documented, and recent attempts to integrate unconventional therapies into conventional medical practices have been widely publicized Pennsylvania physicians have reacted cautiously but are showing increasing interest. This article summarizes the perspectives of physicians who employ at least some of what they prefer to call "complementary" or "adjunctive" therapies-including acupuncture, hypnosis, and herbal remedies.


Immunological and technical considerations in application of alginate-based microencapsulation systems.
Islets encapsulated in immunoprotective microcapsules are being proposed as an alternative for insulin therapy for treatment of type 1 diabetes. Many materials for producing microcapsules have been proposed but only alginate does currently qualify as ready for clinical application. However, many different alginate-based capsule systems do exist. A pitfall in the field is that these systems are applied without a targeted strategy with varying degrees of success as a consequence. In the current review, the different properties of alginate-based systems are reviewed in view of future application in humans. The use of allogeneic and xenogeneic islet sources are discussed with acknowledging the different degrees of immune protection the encapsulation system should supply. Also issues such as oxygen supply and the role of danger associated molecular patterns (DAMPS) in immune activation are being reviewed. A common property of the encapsulation systems is that alginates for medical application should have an extreme high degree of purity and lack pathogen-associated molecular patterns (PAMPs) to avoid activation of the recipient's immune system. Up to now, non-inflammatory alginates are only produced on a lab-scale and are not yet commercially available. This is a major pitfall on the route to human application. Also the lack of predictive pre-clinical models is a burden. The principle differences between relevant innate and adaptive immune responses in humans and other species are reviewed. Especially, the extreme differences between the immune system of non-human primates and humans are cumbersome as non-human primates may not be predictive of the immune responses in humans, as opposed to the popular belief of regulatory agencies. Current insight is that although the technology is versatile major research efforts are required for identifying the mechanical, immunological, and physico-chemical requirements that alginate-based capsules should meet for successful human application.


The effect of a tilting seat on back, lower back and legs during sitting work.
The purpose of this study was to examine the possible effects of a tilting seat on the back, lower back and legs. Ten healthy male subjects aged 22-28 performed word-processing operations while sitting on a chair for one hour under two different seating conditions: the rocking condition and the fixed condition. While the subjects were performing the task, measurements of lower leg swelling were taken using bioelectrical impedance plethysmography, and pain scores were recorded every five min for the neck, shoulders, back, lower back, hips and legs. Electromyograms (EMGs) of the back and lower back (at Th5-6, Th8-9, L1-2 and L3-4) were recorded every sec. In addition, the subjects were videotaped while using the rocking seat, in order to analyze the angle and frequency of seat tilting. At the end of the experiment, the subjects were asked to evaluate the two conditions with respect to localized fatigue and operational efficiency. There was no significant difference in lower leg swelling between the two conditions. EMGs were significantly different at Th5-6, Th8-9 and L1-2 between the two conditions. The rocking condition generated greater EMGs at Th5-6 and L1-2, whereas the fixed condition produced greater EMGs at Th8-9. The pain scores for the neck, shoulders, back and lower back were higher under the fixed condition, while those for the buttocks were higher under the rocking condition. The average tilting frequency was as low as 25.2 times per hour, with 15.6 times per hour for tilting angles ranging from 1 to 2 degrees, and 9.6 times per hour for tilting angles exceeding 2 degrees. As for the subjective evaluations of localized fatigue, seven of the ten subjects preferred the rocking condition, while two preferred the fixed condition and one subject had no preference. Thus, there was a significant difference in the subjective evaluations of the two chairs. These findings suggest that the rocking condition, in contrast to the fixed seating condition, reduced back and lower back pain as a result of its tilting capability. The results of EMGs suggest that the rocking condition reduced back and lower back pain by increasing the overall muscle activity of the back and lower back. The leg impedance measurements showed no effect of the rocking condition on the leg swelling, as compared with the fixed condition.


DPFF-1 transcription factor deficiency causes the aberrant activation of MPK-1 and meiotic defects in the Caenorhabditis elegans germline.
The d4 family of transcription factors consists of three members in mammals. DPF1/neuro-d4 is expressed mainly in neurons and the peripheral nervous system, and is important for brain development. DPF2/requiem/ubi-d4 is expressed ubiquitously and presumably functions as an apoptotic factor, especially during the deprivation of trophic factors. DPF3/cer-d4 is expressed in neurons and in the heart, and is important for heart development and function in zebrafish. In Drosophila, there is only one member, dd4, whose function is still unknown, but it is expressed in many tissues and is particularly abundant in the brain of developing embryos and in adults. Here, we present DPFF-1, the only member of this family of proteins in the nematode C. elegans. DPFF-1 is similar to its mammalian homolog DPF2/requiem/ubi-d4 because it is ubiquitously expressed during embryogenesis and in adult tissues, and because it is important for the induction of germ cell apoptosis during stress. Here, we show that dpff-1 null mutant animals produce less progeny than wild-type nematodes, presumably due to meiotic defects. Gonads of dpff-1 deficient animals showed more germ cells in pachytene and overexpressed the P-MPK-1 signal. Additionally, these animals presented higher levels of p53-induced germ cell apoptosis than wild-type animals. Furthermore, we observed that dpff-1 deficient animals are more sensitive to heat shock. This is the first report showing that the d4 family of transcription factors could be involved in meiosis and stress protection.


Non-invasive prenatal testing: ethics and policy considerations.
New technologies analyzing fetal DNA in maternal blood have led to the wide commercial availability of non-invasive prenatal testing (NIPT). We present here for clinicians the ethical and policy issues related to an emerging practice option. Although NIPT presents opportunities for pregnant women, particularly women who are at increased risk of having a baby with an abnormality or who are otherwise likely to access invasive prenatal testing, NIPT brings significant ethics and policy challenges. The ethical issues include multiple aspects of informed decision-making, such as access to counselling about the possible results of the test in advance of making a decision about participation in NIPT. Policy considerations include issues related to offering and promoting a privately available medical strategy in publicly funded institutions. Ethics and policy considerations merge in NIPT with regard to sex selection and support for persons living with disabilities.


Establishment of murine endothelial cell lines that develop angiosarcomas in vivo: brief demonstration of a proposed animal model for Kaposi's sarcoma.
We have reported previously that 100% of the incidence of malignant endotheliomas and angiosarcomas was developed in specific-pathogen-free BALB/c mice given s.c. injections of 1,2-dimethylhydrazine dihydrochloride. These tumors appeared selectively in the liver. In the present study, we have successfully established two cell lines in vitro (D10 and D14) from some of these tumors and have characterized the biological features of these lines. D10 and D14 have a 24- to 26-h doubling time and show a spindle formation in confluent monolayer cultures. The D10 line has a low capability of anchorage-independent growth in soft agar as well as less tumorigenicity in syngeneic mice. When as many as 10(7) D10 cells were injected s.c. into syngeneic mice, only one-half of the mice developed tumors composed of neoplastic endothelial cells with ample vascular lumina of various sizes. The histological appearance of this tumor resembled that of Kaposi's sarcoma as a human counterpart. The D14 line, in contrast, has a relatively high capability to grow in the soft agar culture. However, the tumor growth in vivo was less tumorigenic. None of the mice given injections of less than 10(6) D14 cells developed tumors. Although all of mice given injections of 10(7) D14 cells developed tumors, these tumors regressed completely until the 6th week after inoculation, suggesting that these cells were immunogenic in the transplantation assays using syngeneic mice. These lines may provide useful information for the study of cytological features of vascular tumors.


[The role of stromal cell-derived factor and its receptor-CXCR4 in G-CSF-induced hematopoietic stem cell mobilization].
To explore the role of stromal cell-derived factor (SDF-1) and its specific receptor CXCR4 in the G-CSF-induced hematopoietic stem/progenitor cells (HSPCs) mobilization in human healthy donor. The changes of SDF-1/CXCR4 in bone marrow (BM) and peripheral blood (PB) of healthy donors during G-CSF-induced mobilization were detected by enzyme-linked immunosorbent assay (ELISA), immunohistological staining and flow cytometry. SDF-1 neutralizing antibody wes injected into BALB/c mice to further test its effect on mobilization. SDF-1 concentration in mobilized BM (mBM), steady state BM (ssBM) and PB were(7.23 +/- 0.66) microg/L, (5.43 +/- 0.35) microg/L and (5.42 +/- 0.52) microg/L, respectively. SDF-1 protein levels were decreased in the BM (P < 0.05) after 5-day G-CSF injection, and its concentration gradient between BM and PB disappeared (P > 0.05). Significant up-regulation of CXCR4 expression was observed on mBM CD34 cells in healthy donors. The rate of CXCR4 expression on CD34 cells in ssBM, mBM and mobilized PB were (40.98 +/- 21.56)%, (65.80 +/- 24.68)% and (27.54 +/- 26.03)%, respectively. Comparing with that in ssBM and mBM, CXCR4 expression on mobilized PB CD34+ cells were significantly decreased (P < 0.05). Inhibition of SDF-1 signal by blocking monoclonal antibodies significantly reduced G-CSF-induced mobilization in BALB/c mice. This resulted in significant decrease of white blood cell count and progenitors mobilized into peripheral circulation. G-CSF induces HSPCs mobilization by decreasing bone marrow SDF-1 and down-regulating CXCR4 expression on HSPCs.


Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms.
Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease.


Online gallery facilitated art activities for people with dementia during the COVID-19 pandemic and beyond: A narrative review.
Art activities for people with dementia have a range of therapeutic benefits including psychosocial wellbeing and enhanced quality of life. Successful art programs promote social engagement, are inclusive and empowering, and enable opportunity for people with dementia to express themselves verbally and non-verbally. The COVID-19 pandemic and associated social distancing precautions have impacted the capacity of art galleries and museums to deliver in-person programs. However, they have also provided a new opportunity. This paper explores the potential benefits, challenges, and future directions for research relating to the online delivery of gallery-facilitated art activities for people with dementia. The evidence revealed that increased digitisation of programs increased access for participants, however, the majority of the research was published before the pandemic. Nevertheless, COVID-19 has necessitated many museums and galleries to engage with people with dementia online. Future research is needed to improve the usability of online delivery platforms and a comparison of online and onsite delivery is recommended, particularly to evaluate benefits to people living in rural and remote areas where access to museums and galleries may be limited.


Maladjusted host immune responses induce experimental cerebral malaria-like pathology in a murine Borrelia and Plasmodium co-infection model.
In the Plasmodium infected host, a balance between pro- and anti-inflammatory responses is required to clear the parasites without inducing major host pathology. Clinical reports suggest that bacterial infection in conjunction with malaria aggravates disease and raises both mortality and morbidity in these patients. In this study, we investigated the immune responses in BALB/c mice, co-infected with Plasmodium berghei NK65 parasites and the relapsing fever bacterium Borrelia duttonii. In contrast to single infections, we identified in the co-infected mice a reduction of L-Arginine levels in the serum. It indicated diminished bioavailability of NO, which argued for a dysfunctional endothelium. Consistent with this, we observed increased sequestration of CD8+ cells in the brain as well over expression of ICAM-1 and VCAM by brain endothelial cells. Co-infected mice further showed an increased inflammatory response through IL-1β and TNF-α, as well as inability to down regulate the same through IL-10. In addition we found loss of synchronicity of pro- and anti-inflammatory signals seen in dendritic cells and macrophages, as well as increased numbers of regulatory T-cells. Our study shows that a situation mimicking experimental cerebral malaria (ECM) is induced in co-infected mice due to loss of timing and control over regulatory mechanisms in antigen presenting cells.


Plasma clearance, transfer, and distribution of vitamin D3 from intestinal lymph.
The clearance of vitamin D3 from plasma after intravenous injection to rats of intestinal lymph labeled in vivo with radioactive vitamin D3 has been studied. The half-life of the injected vitamin D3 was about 6 min. In double-label experiments the half-life was the same for vitamin D3 as for vitamin A, which is removed from the circulation as chylomicron remnants. Fractionation of the blood plasma according to the density showed that 2 min after the injection of the lymph 30-95% of the radioactive vitamin D3 was recovered in plasma fractions with higher densities than chylomicron remnants (d greater than 1.019 g/ml). The percentage of vitamin D3 in the chylomicron fraction (d less than 1.006 g/ml) of the injected lymph was 66-95%. Taking this into account it could be calculated that the amount of radioactive vitamin D3 transferred from chylomicrons or chylomicron remnants to plasma with d greater than 1.019 g/ml within 2 min varied from 26 to 72%. The transferred radioactivity was recovered in a protein fraction with chromatographic mobilities identical to the binding protein for vitamin D and its metabolites. During the first 13 min after injection the amount of radioactivity recovered in the liver was less than 10%, but from 15 to 55 min the amount increased to about 50% of the injected dose. These findings suggest that the transfer of vitamin D3 from chylomicrons to the alpha-globulin fraction previously observed in vitro is of importance for the in vivo handling of vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)


Monovision and LASIK.
Many LASIK patients are early and mid-presbyopes. Monovision is commonly targeted for these patients because of demographics. Considerations are reduced stereopsis, reduced acuity, night driving, and liability. Case studies are used to illustrate contact lens and alternative trials for presbyopic and prepresbopic monovision LASIK patients. A preoperative monovision contact lens trial can be used to demonstrate monovision effects to the candidate for refractive surgery. Selection of add power, selection of distance and near eye, residual astigmatism, management, and gradual transistioning with regards to adaptation are discussed.


Semi-Automatic Assessment of Vocalization Quality for Children With and Without Angelman Syndrome.
Automated methods for processing of daylong audio recordings are efficient and may be an effective way of assessing developmental stage for typically developing children; however, their utility for children with developmental disabilities may be limited by constraints of algorithms and the scope of variables produced. Here, we present a novel utterance-level processing (ULP) system that 1) extracts utterances from daylong recordings, 2) verifies automated speaker tags using human annotation, and 3) provides vocal maturity metrics unavailable through automated systems. Study 1 examines the reliability and validity of this system in low-risk controls (LRC); Study 2 extends the ULP to children with Angelman syndrome (AS). Results showed that ULP annotations demonstrated high coder agreement across groups. Further, ULP metrics aligned with language assessments for LRC but not AS, perhaps reflecting limitations of language assessments in AS. We argue that ULP increases accuracy, efficiency, and accessibility of detailed vocal analysis for syndromic populations.


Understanding Impacts of Online Dual Practice on Health System Performance: A Qualitative Study in China.
The outbreak of the COVID-19 pandemic has boosted the global development of online healthcare platforms. An increasing number of public hospital doctors are providing online services on private third-party healthcare platforms, creating a new form of dual practice-online dual practice. To explore the impacts of online dual practice on health system performance as well as potential policy responses, we undertook a qualitative approach that uses in-depth interviews and thematic analysis. Following a purposive sampling, we interviewed 57 Chinese respondents involved in online dual practice. We asked respondents for their opinions on the effects of online dual practice on access, efficiency, quality of care, and advice on regulatory policy. The results suggest that online dual practice can generate mixed impacts on health system performance. The benefits include improved accessibility due to increased labor supply of public hospital doctors, better remote access to high-quality services, and lower privacy concerns. It can improve efficiency and quality by optimizing patient flows, reducing repetitive tasks, and improving the continuity of care. However, the potential distraction from designated work at public hospitals, inappropriate use of virtual care, and opportunistic physician behaviors may undermine overall accessibility, efficiency, and quality. Countries should mitigate these adverse consequences via regulations that are appropriate to their healthcare system context, policy priority, and governance capacity.


Health risks associated with crude oil spill exposure.
Human exposure to crude oil spills is associated with multiple adverse health effects including hematopoietic, hepatic, renal, and pulmonary abnormalities. The purpose of this study was to assess the hematological and liver function indices among the subjects participating in the Gulf oil spill cleanup operations in comparison with the standardized normal range reference values. Using medical charts, clinical data (including white blood cell [WBC] count, platelet count, hemoglobin, hematocrit, blood urea nitrogen [BUN] creatinine, alkaline phosphatase [ALP], aspartate amino transferase [AST], alanine amino transferase [ALT], and urinary phenol) were gathered for the subjects who were exposed to the Gulf oil spill and analyzed. A total of 117 subjects exposed to the oil spill were included. Over 77% of subjects had WBC counts in the mid range (6-10 × 10(3) per μL), while none of the subjects had the upper limit of the normal range (11 × 10(3) per μL). A similar pattern was seen in the platelet counts and BUN levels among the oil spill-exposed subjects. Conversely, over 70% of the subjects had creatinine levels toward the upper limit of the normal range and 23% of subjects had creatinine levels above the upper limit of the normal range (>1.3 mg per dL). Similarly, hemoglobin and hematocrit levels were toward the upper limit of normal in more than two thirds of the subjects. AST and ALT levels above the upper limit of normal range (>40 IU per L) were seen in 15% and 31% of subjects, respectively. Over 80% of subjects had urinary phenol levels higher than detectable levels (2 mg per L). The results of this study support our earlier study findings in which we found that people who participated in oil spill cleanup activities are at risk of developing alterations in hematological profile and liver function.


Substitution of PFAS chemistry in outdoor apparel and the impact on repellency performance.
Intensifying legislation and increased research on the toxicological and persistent nature of per- and polyfluoroalkyl substances (PFASs) have recently influenced the direction of liquid repellent chemistry use; environmental, social, and sustainability responsibilities are at the crux. Without PFAS chemistry, it is challenging to meet current textile industry liquid repellency requirements, which is a highly desirable property, particularly in outdoor apparel where the technology helps to provide the wearer with essential protection from adverse environmental conditions. Herein, complexities between required functionality, legislation and sustainability within outdoor apparel are discussed, and fundamental technical performance of commercially available long-chain (C8) PFASs, shorter-chain (C6) PFASs, and non-fluorinated repellent chemistries finishes are evaluated comparatively. Non-fluorinated finishes provided no oil repellency, and were clearly inferior in this property to PFAS-finished fabrics that demonstrated good oil-resistance. However, water repellency ratings were similar across the range of all finished fabrics tested, all demonstrating a high level of resistance to wetting, and several non-fluorinated repellent fabrics provide similar water repellency to long-chain (C8) PFAS or shorter-chain (C6) PFAS finished fabrics. The primary repellency function required in outdoor apparel is water repellency, and we would propose that the use of PFAS chemistry for such garments is over-engineering, providing oil repellency that is in excess of user requirements. Accordingly, significant environmental and toxicological benefits could be achieved by switching outdoor apparel to non-fluorinated finishes without a significant reduction in garment water-repellency performance. These conclusions are being supported by further research into the effect of laundering, abrasion and ageing of these fabrics.


Successfully Recruiting Adults with a Low Socioeconomic Position into Community-Based Lifestyle Programs: A Qualitative Study on Expert Opinions.
We explored experts' perceived challenges and success factors in the recruitment of adults with a low socioeconomic position (SEP) for participation in community-based lifestyle modification programs. We conducted semi-structured interviews with 11 experienced project coordinators, based on a topic list that included experiences with recruitment, perceived barriers and success factors, and general views on recruitment strategies. Results revealed challenges related to the context of the program (e.g., limited program resources), psychosocial barriers of the participants (e.g., mistrust or skepticism), practical barriers (e.g., low literacy or having other priorities), and reasons to decline participation (e.g., lack of interest or motivation). Success factors were related to securing beneficial contextual and program-related factors (e.g., multi-layered recruitment strategy), establishing contact with the target group (e.g., via existing networks, community key-members), methods to increase engagement (e.g., personal approach and involvement of the target group in the program process) and making participation easier (e.g., providing transport), and providing various types of incentives. Concluding, the group of participants with low SEP covers a wide spectrum of individuals. Therefore, multiple recruitment strategies at multiple layers should be employed, and tailored. The lessons learned of those with hands-on experiences will help to enhance recruitment in future programs.


A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway.
Binding of microRNA (miRNA) to mRNA within the RNA-induced silencing complex (RISC) leads to either translational inhibition or to destruction of the target mRNA. Both of these functions are executed by Argonaute 2 (Ago2). Using hematopoiesis in mice as a model system to study the physiological function of Ago2 in vivo, we found that Ago2 controls early development of lymphoid and erythroid cells. We show that the unique and defining feature of Ago2, the Slicer endonuclease activity, is dispensable for hematopoiesis. Instead, we identified Ago2 as a key regulator of miRNA homeostasis. Deficiency in Ago2 impairs miRNA biogenesis from precursor-miRNAs followed by a reduction in miRNA expression levels. Collectively, our data identify Ago2 as a highly specialized member of the Argonaute family with an essential nonredundant Slicer-independent function within the mammalian miRNA pathway.


Effect of weight-bearing activities on bone mineral density in spinal cord injured patients during the period of the first two years.
Prospective study on patients with spinal cord injuries. To evaluate the loss of bone mineral density (BMD) in various body regions of patients with spinal cord injury (SCI) and its dependence on weight bearing activities during 2 years post injury. BMD of the whole body was measured in patients with SCI. Baseline measurement was performed in 6-16 weeks after SCI, the second and the third-respectively 12 and 24 months after injury. Fifty-four subjects were selected and divided into two groups: standing and non-standing. From these groups 27 pairs were made according to gender, age and height. There was found to be a well-marked decrease in BMD values for lower extremities, but there was no significant difference between paraplegic and tetraplegic patients 1 and 2 year after injury. Leg BMD reduced by 19.62% (95% CI, 17-22%) in the standing group and by 24% (95% CI, 21-27%) in non-standing group during the first year. Two years after SCI patients in standing group had significantly higher leg BMD-1.018 g/cm(2) (95% CI, 0.971-1.055 g/cm(2)) than in the non-standing group-0.91 g/cm(2) (95% CI, 0.872-0.958 g/cm(2)) (P<or=0.0001). SCI patients who performed daily standing >or=1 h and not less than 5 days per week, had significantly higher BMD in the lower extremities after 2 years in comparison to those patients who did not perform standing.


In situ lipidomics of Staphylococcus aureus osteomyelitis using imaging mass spectrometry.
Osteomyelitis occurs when Staphylococcus aureus invades the bone microenvironment, resulting in a bone marrow abscess with a spatially defined architecture of cells and biomolecules. Imaging mass spectrometry and microscopy are invaluable tools that can be employed to interrogate the lipidome of S. aureus -infected murine femurs to reveal metabolic and signaling consequences of infection. Here, nearly 250 lipids were spatially mapped to healthy and infection-associated morphological features throughout the femur, establishing composition profiles for tissue types. Ether lipids and arachidonoyl lipids were significantly altered between cells and tissue structures in abscesses, suggesting their roles in abscess formation and inflammatory signaling. Sterols, triglycerides, bis(monoacylglycero)phosphates, and gangliosides possessed ring-like distributions throughout the abscess, indicating dysregulated lipid metabolism in a subpopulation of leukocytes that cannot be discerned with traditional microscopy. These data provide chemical insight into the signaling function and metabolism of cells in the fibrotic border of abscesses, likely characteristic of lipid-laden macrophages.


Comparison of Broad vs Narrow Focal Width Lithotripter Fields.
To investigate the impact of lithotripter focal width on stone fragmentation. A modified reflector was used to reduce -6 dB beam size of the HM3 lithotripter, while increasing concomitantly peak pressure. Fragmentation in vitro was assessed with modified and original reflectors using BegoStone phantoms. A membrane holder was used to mimic lithotripsy in vivo, and a matrix holder was used to assess variations of fragmentation power in the focal plane of the lithotripter field. Stone fragmentation in vivo produced by the two reflectors was further compared in a swine model. Stone fragmentation in vitro after 500 (or 2000) shocks was ∼60% (or ∼82%) vs ∼40% (or ∼75%) with original and modified reflector, respectively (p ≤ 0.0016). Fragmentation power with the modified reflector was the highest on the lithotripter axis, but dropped rapidly in the lateral direction and became insignificant at radial distances >6.0 mm. Stone fragmentation with the original reflector was lower along the lithotripter axis, but fragmentation power decayed slowly in lateral direction, with appreciable fragmentation produced at 6.0 mm. Stone fragmentation efficiency in vivo after 500 (or 2000) shocks was ∼70% (or ∼90%) vs ∼45% (or ∼80%) with original and modified reflector, respectively (p ≤ 0.04). A lithotripter field with broad beam size yields superior stone comminution when compared with narrow beam size under comparable effective acoustic pulse energy both in vivo and in vitro. These findings may facilitate future improvements in lithotripter design to maximize comminution efficiency while minimizing tissue injury.


Opposite regiospecific ring opening of 2-(cyanomethyl)aziridines by hydrogen bromide and benzyl bromide: experimental study and theoretical rationalization.
Ring opening of 1-arylmethyl-2-(cyanomethyl)aziridines with HBr afforded 3-(arylmethyl)amino-4-bromobutyronitriles via regiospecific ring opening at the unsubstituted aziridine carbon. Previous experimental and theoretical reports show treatment of the same compounds with benzyl bromide to furnish 4-amino-3-bromobutanenitriles through ring opening at the substituted aziridine carbon. To gain insights into the regioselective preference with HBr, reaction paths have been analyzed with computational methods. The effect of solvation was taken into account by the use of explicit solvent molecules. Geometries were determined at the B3LYP/6-31++G(d,p) level of theory, and a Grimme-type correction term was included for long-range dispersion interactions; relative energies were refined with the meta-hybrid MPW1B95 functional. Activation barriers confirm preference for ring opening at the unsubstituted ring carbon for HBr. HBr versus benzyl bromide ring opening was analyzed through comparison of the electronic structure of corresponding aziridinium intermediates. Although the electrostatic picture fails to explain the opposite regiospecific nature of the reaction, frontier molecular orbital analysis of LUMOs and nucleophilic Fukui functions show a clear preference of attack for the substituted aziridine carbon in the benzyl bromide case and for the unsubstituted aziridine carbon in the HBr case, successfully rationalizing the experimentally observed regioselectivity.


Functional vision in patients with neovascular maculopathy and poor visual acuity.
Central visual function is characteristically reported as Snellen acuity at distance and near. We performed functional tests in a group of patients with visual acuity of 20/100 or worse due to macular disease to determine whether there was a relationship between Snellen acuity and functional performance among these patients with poor visual acuity. Our tests of functional performance included currency discrimination, color recognition, reading a clock, and reading large print. Our results suggest that there is a correlation between Snellen acuity and functional vision, even among patients with poor visual acuity. Hence, therapeutic efforts to keep patients' visual acuity at 20/200 rather than 20/400, for example, appears to be justifiable in that better acuity levels seem to be associated with improved functional performance.


Conditional PPARγ knockout from cardiomyocytes of adult mice impairs myocardial fatty acid utilization and cardiac function.
While the roles of PPARα and PPARδ (β) in transcriptional regulation of myocardial lipid metabolisms are well established, an essential role of PPARγ in regulating lipid metabolisms in the adult heart remains unclear. In this study, we investigated whether PPARγ is required for normal myocardial lipid metabolism at basal condition in adult mice. We assessed the short-term cardiomyocyte-restricted PPARγ knockout mice with a Tamoxifen inducible Cre-LoxP mediated gene targeting strategy. The expression of PPARγ mRNA and protein in cardiomyocytes of adult mice was substantially reduced after short-term induction. Transcript and protein levels of important proteins in fatty acid uptake and oxidation, such as CD36, heart type-fatty acid binding protein (FABP), and carnitine palmitoyltransferase I (CPT-I) were reduced in the PPARγ deficient hearts. Myocardial fatty acid utilization and cardiac contraction were depressed in PPARγ deficient hearts. The PPARγ deficient hearts exhibited modest cardiac hypertrophy compared with controls. These results indicate that PPARγ is a transcription factor that is required for basal myocardial fatty acid utilization in the adult heart.


Education and implementation of home spirometry in an adolescent cystic fibrosis population.
Lung function in individuals with cystic fibrosis (CF) is closely monitored as an objective marker of clinical status. The COVID-19 pandemic shifted our ability to assess individuals from in-person to remote monitoring using telehealth. As part of efforts to monitor individuals remotely during this time, this study describes the process of education and implementation of home spirometry in an adolescent CF population at Nemours Children's Hospital in Wilmington, Delaware, USA. In addition, this study reviews the ability of adolescents with CF to produce reliable, consistent, and accurate results using home spirometry. This was a quality-improvement study over a 9-month period at a single CF center. Home spirometers were supplied by the CF Foundation to 40 adolescents with CF. An educational curriculum was used for initial training on the device by a dedicated CF respiratory therapist. After training, participants reported spirometry results weekly until reliable technique was established. Once reliable technique was achieved, participants reported results monthly. Results were retrospectively reviewed to determine accuracy and consistency. The percentages of patients who were able to achieve reliable, consistent, and accurate results were recorded as well as the need for additional training or other reasons for inability to produce ongoing results. Home spirometers were distributed to 40 adolescents. Out of these 40 participants, 35 (88%) completed initial training; 29 (83%) sent at least one set of results, and 24 (60%) established reliable technique after an average of 5 weekly attempts. When home spirometer results were retrospectively reviewed, 83% (20/24) were deemed accurate in comparison to spirometry completed in clinic, and 83% (20/24) showed consistency between efforts sent. Home spirometry, when properly implemented with structured education and active participant engagement, has potential to provide meaningful data and feedback to CF care teams. Implementation of this process requires substantial resources and active participation from an adolescent population who are at higher risk for non-adherence. Future studies are needed to determine the impact of home spirometry on clinical outcomes and reliability over time and to address barriers to consistent and enduring engagement in the adolescent population.


Nematococcomyces rhododendri, a new species in a new genus of the Rhytismatales from China.
A fungus belonging to the Rhytismatales found on twigs of Rhododendron lutescens in Yunnan, southwestern China, is described as a new species in a new genus. It is characterized by Coccomyces-like ascomata but differs in having elliptical ascospores with filiform, hyaline appendages. The ascospores of this new taxon are somewhat similar to those of species of Parvacoccum, but the latter has symmetrical, fusiform ascospores with funnel-shaped appendages. The new genus also is distinct from Hypoderma, Hypodermella, Myriophacidium, Ploioderma, Neococcomyces and Therrya.