Novel At-Home Mother's Milk Conductivity Sensing Technology as an Identification System of Delay in Milk Secretory Activation Progress and Early Breastfeeding Problems: Feasibility Assessment.
Prolonged exclusive breastfeeding is a public health priority and a personal desire by mothers; however, rates are low with milk supply challenges as a predominant cause. Early breastfeeding management at home is key. Milk electrolytes, mainly sodium ions, are accepted as biomarkers of secretory activation processes throughout the first weeks after birth and predictors for prolonged breastfeeding success, although they are not incorporated into routine care practice. The aim of this study was to test the feasibility of a novel handheld smartphone-operated milk conductivity sensing system that was designed to compute a novel parameter, milk maturation percent (MM%), calculated from milk sample conductivity for tracking individual secretory activation progress in a real-world home setting. System performance was initially evaluated in data collected from laboratory-based milk analysis, followed by a retrospective analysis of observational real-world data gathered with the system, on the spot in an at-home setting, implemented by lactation support providers or directly by mothers (N=592). Data collected included milk sample sensing data, baby age, and self-reported breastfeeding status and breastfeeding-related conditions. The data were retroactively classified in a day after birth-dependent manner. Results were compared between groups classified according to breastfeeding exclusivity and breastfeeding problems associated with ineffective breastfeeding and low milk supply. Laboratory analysis in a set of breast milk samples demonstrated a strong correlation between the system's results and sodium ion levels. In the real-world data set, a total of 1511 milk sensing records were obtained on the spot with over 592 real-world mothers. Data gathered with the system revealed a typical time-dependent increase in the milk maturation parameter (MM%), characterized by an initial steep increase, followed by a moderate increase, and reaching a plateau during the first weeks postpartum. Additionally, MM% levels captured by the system were found to be sensitive to breastfeeding status classifications of exclusive breastfeeding and breastfeeding problems, manifested by differences in group means in the several-day range after birth, predominantly during the first weeks postpartum. Differences could also be demonstrated for the per-case time after birth-dependent progress in individual mothers. This feasibility study demonstrates that the use of smart milk conductivity sensing technology can provide a robust, objective measure of individual breastfeeding efficiency, facilitating remote data collection within a home setting. This system holds considerable potential to augment both self-monitoring and remote breastfeeding management capabilities, as well as to refine clinical classifications. To further validate the clinical relevance and potential of this home milk monitoring tool, future controlled clinical studies are necessary, which will provide insights into its impact on user and care provider satisfaction and its potential to meet breastfeeding success goals.


Islet amyloglucosidase activity: some characteristics, and its relation to insulin secretion stimulated by various secretagogues.
The glucose-producing amylolytic activity in pancreatic islet tissue was characterized with regard to its properties with glycogen (amyloglucosidase) and maltose (maltase) as substrate, its optimum activity in islets from different strains of mice (NMRI, CBA and C-57BL) and after fasting, and its relation to the insulin secretory response after different secretagogues in vivo. Additionally the effects and fate of injected fungal acid amyloglucosidase were assessed. In the pancreatic islets of NMRI mice both the glycogen-splitting activity and the maltose-splitting activity displayed latency and an acid pH-optimum of about 5.0. After differential centrifugation a significant part of amyloglucosidase activity was found to be confined to the mitochondrial-lysosomal fraction. In crude islet homogenate the apparent Km for maltose at pH 5.0 was 2.1 mM. No Km for glycogen could be given because of complex kinetics in the presence of this substrate. The maltase activity was about 30% lower than the amyloglucosidase activity in islet tissue from NMRI mice. The reverse pattern was observed in the liver. Moreover, the liver amyloglucosidase activity was only one fourth of that of the islet tissue. The amyloglucosidase but not the maltase activity in islet tissue from CBA mice was lower than in islets from NMRI mice. Both activities were very low in islets from C-57 mice. A 24 hr fasting period reduced the amyloglucosidase but not the maltase activity in islets from NMRI mice. The insulin secretory response in vivo to an i.v. arginine load in the different strains and after fasting displayed the same pattern as the islet amyloglucosidase activity, whereas the insulin response following a glucagon injection was largest in the C-57 strain and unaffected by the fasting state. Pretreatment of mice with 0.05 mumol/kg of highly purified fungal amyloglucosidase, moderately (about 35%) enhanced the insulin secretory response to arginine, did not affect the response to glucagon, and greatly (about 100%) enhanced the response to glucose and tolbutamide. Moreover, treatment of mice with lysosomal stabilizers (glucocorticoids) reduced the insulin response to sulphonylureas and glucose, had no effect on the insulin response to beta-adrenergic and cholinergic stimulation, and increased ACTH-induced insulin release. A lysosomal labilizer (progesterone) enhanced the insulin response induced by glucose and tolbutamide.(ABSTRACT TRUNCATED AT 400 WORDS)


Pd-catalyzed silicon hydride reductions of aromatic and aliphatic nitro groups.
[reaction: see text] Room-temperature reduction of aromatic nitro groups to amines can be accomplished in high yield, with wide functional group tolerance and short reaction times (30 min) using a combination of palladium(II) acetate, aqueous potassium fluoride, and polymethylhydrosiloxane (PMHS). Replacing PMHS/KF with triethylsilane allows aliphatic nitro groups to be reduced to their hydroxylamines.


Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma.
Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8+ TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNγ) and CD8+ gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNγ stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.


Effects of dietary Bacillus amyloliquefaciens supplementation on growth performance, intestinal morphology, inflammatory response, and microbiota of intra-uterine growth retarded weanling piglets.
The focus of recent research has been directed toward the probiotic potential of Bacillus amyloliquefaciens (BA) on the gut health of animals. However, little is known about BA's effects on piglets with intra-uterine growth retardation (IUGR). Therefore, this study investigated the effects of BA supplementation on the growth performance, intestinal morphology, inflammatory response, and microbiota of IUGR piglets. Eighteen litters of newborn piglets were selected at birth, with one normal birth weight (NBW) and two IUGR piglets in each litter (i.e., 18 NBW and 36 IUGR piglets in total). At weaning, the NBW piglet and one of the IUGR piglets were assigned to groups fed a control diet (i.e., the NBW-CON and IUGR-CON groups). The other IUGR piglet was assigned to a group fed the control diet supplemented with 2.0 g BA per kg of diet (i.e., IUGR-BA group). The piglets were thus distributed across three groups for a four-week period. IUGR reduced the growth performance of the IUGR-CON piglets compared with the NBW-CON piglets. It was also associated with decreased villus sizes, increased apoptosis rates, reduced goblet cell numbers, and an imbalance between pro- and anti-inflammatory cytokines in the small intestine. Supplementation with BA improved the average daily weight gain and the feed efficiency of the IUGR-BA group compared with the IUGR-CON group (P < 0.05). The IUGR-BA group exhibited increases in the ratio of jejunal villus height to crypt depth, in ileal villus height, and in ileal goblet cell density. They also exhibited decreases in the numbers of jejunal and ileal apoptotic cells and ileal proliferative cells (P < 0.05). Supplementation with BA increased interleukin 10 content, but it decreased tumor necrosis factor alpha level in the small intestines of the IUGR-BA piglets (P < 0.05). Furthermore, compared with the IUGR-CON piglets, the IUGR-BA piglets had less Escherichia coli in their jejunal digesta, but more Lactobacillus and Bifidobacterium in their ileal digesta (P < 0.05). Dietary supplementation with BA improves morphology, decreases inflammatory response, and regulates microbiota in the small intestines of IUGR piglets, which may contribute to improved growth performance during early life.


Temperature Variability and Mortality: A Multi-Country Study.
The evidence and method are limited for the associations between mortality and temperature variability (TV) within or between days. We developed a novel method to calculate TV and investigated TV-mortality associations using a large multicountry data set. We collected daily data for temperature and mortality from 372 locations in 12 countries/regions (Australia, Brazil, Canada, China, Japan, Moldova, South Korea, Spain, Taiwan, Thailand, the United Kingdom, and the United States). We calculated TV from the standard deviation of the minimum and maximum temperatures during the exposure days. Two-stage analyses were used to assess the relationship between TV and mortality. In the first stage, a Poisson regression model allowing over-dispersion was used to estimate the community-specific TV-mortality relationship, after controlling for potential confounders. In the second stage, a meta-analysis was used to pool the effect estimates within each country. There was a significant association between TV and mortality in all countries, even after controlling for the effects of daily mean temperature. In stratified analyses, TV was still significantly associated with mortality in cold, hot, and moderate seasons. Mortality risks related to TV were higher in hot areas than in cold areas when using short TV exposures (0-1 days), whereas TV-related mortality risks were higher in moderate areas than in cold and hot areas when using longer TV exposures (0-7 days). The results indicate that more attention should be paid to unstable weather conditions in order to protect health. These findings may have implications for developing public health policies to manage health risks of climate change. Guo Y, Gasparrini A, Armstrong BG, Tawatsupa B, Tobias A, Lavigne E, Coelho MS, Pan X, Kim H, Hashizume M, Honda Y, Guo YL, Wu CF, Zanobetti A, Schwartz JD, Bell ML, Overcenco A, Punnasiri K, Li S, Tian L, Saldiva P, Williams G, Tong S. 2016. Temperature variability and mortality: a multi-country study. Environ Health Perspect 124:1554-1559; http://dx.doi.org/10.1289/EHP149.


Gratitude facilitates behavioral mimicry.
Recent theorists argue that gratitude, besides encouraging social exchange, serves an important function of relationship building. However, there is a lack of research exploring the specific behaviors through which gratitude promotes relationship building. Given that behavioral mimicry serves important affiliative needs, we explored whether gratitude promotes behavioral mimicry. We found that participants who received intentional help later mimicked the behavioral mannerisms of their benefactor. This mimicry tendency was not extended to a nonbenefactor. In contrast, participants who ended up with the same positive outcome, but believed that it was attributable to chance, did not exhibit a reliable level of mimicry. Our results suggest that nonconscious behavioral mimicry might be a subtle but important first step through which gratitude promotes communal relationships.


Developmental phonagnosia: Linking neural mechanisms with the behavioural phenotype.
Human voice recognition is critical for many aspects of social communication. Recently, a rare disorder, developmental phonagnosia, which describes the inability to recognise a speaker's voice, has been discovered. The underlying neural mechanisms are unknown. Here, we used two functional magnetic resonance imaging experiments to investigate brain function in two behaviourally well characterised phonagnosia cases, both 32 years old: AS has apperceptive and SP associative phonagnosia. We found distinct malfunctioned brain mechanisms in AS and SP matching their behavioural profiles. In apperceptive phonagnosia, right-hemispheric auditory voice-sensitive regions (i.e., Heschl's gyrus, planum temporale, superior temporal gyrus) showed lower responses than in matched controls (nAS=16) for vocal versus non-vocal sounds and for speaker versus speech recognition. In associative phonagnosia, the connectivity between voice-sensitive (i.e. right posterior middle/inferior temporal gyrus) and supramodal (i.e. amygdala) regions was reduced in comparison to matched controls (nSP=16) during speaker versus speech recognition. Additionally, both cases recruited distinct potential compensatory mechanisms. Our results support a central assumption of current two-system models of voice-identity processing: They provide the first evidence that dysfunction of voice-sensitive regions and impaired connectivity between voice-sensitive and supramodal person recognition regions can selectively contribute to deficits in person recognition by voice.


Tumor-suppressive microRNA-206 as a dual inhibitor of MET and EGFR oncogenic signaling in lung squamous cell carcinoma.
Expression of the oncogene hepatocyte growth factor receptor (MET) and phosphorylation of the MET protein have been associated with both primary and acquired resistance to tyrosine kinase inhibitors (TKIs) used in therapy targeting the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancers (NSCLCs). Therefore, simultaneous inhibition of both of these receptor tyrosine kinases (RTKs) should improve disease treatment. Our previous study of microRNA (miRNA) expression signatures of lung squamous cell carcinoma (lung-SCC) revealed that microRNA-206 (miR‑206) was significantly reduced in lung-SCC tissues, suggesting that miR‑206 functions as a tumor suppressor in the disease. Furthermore, putative miR‑206 binding sites were annotated in the 3'-UTRs of MET and EGFR RTKs in miRNA databases. The aim of the study was to investigate the functional significance of miR‑206 in lung-SCC and to confirm the inhibition of both MET and EGFR oncogenic signaling by expression of miR‑206 in cancer cells. We found that restoration of mature miR‑206 inhibited cancer cell proliferation, migration, and invasion in EBC-1 cells through downregulation of both mRNA and protein levels of MET and EGFR. Interestingly, phosphorylation of ERK1/2 and AKT signaling were inhibited by restoration of miR‑206 in cancer cells. Overexpression of MET and EGFR were observed in clinical specimens of lung-SCC. Tumor-suppressive miR‑206 inhibited dual signaling networks activated by MET and EGFR, and these findings will provide new insights into the novel molecular mechanisms of lung-SCC oncogenesis and new therapeutic approaches for the treatment of this disease.


Comparative analysis of gonadal transcriptomes between turtle and alligator identifies common molecular cues activated during the temperature-sensitive period for sex determination.
The mode of sex determination in vertebrates can be categorized as genotypic or environmental. In the case of genotypic sex determination (GSD), the sexual fate of an organism is determined by the chromosome composition with some having dominant genes, named sex-determining genes, that drive the sex phenotypes. By contrast, many reptiles exhibit environmental sex determination (ESD), whereby environmental stimuli drive sex determination, and most notably temperature. To date, temperature-dependent sex determination (TSD) has been found in most turtles, some lizards, and all crocodylians, but commonalities in the controlling processes are not well established. Recent innovative sequencing technology has enabled investigations into gonadal transcriptomic profiles during temperature-sensitive periods (TSP) in various TSD species which can help elucidate the controlling mechanisms. In this study, we conducted a time-course analysis of the gonadal transcriptome during the male-producing temperature (26℃) of the Reeve's turtle (Chinese three-keeled pond turtle) Mauremys reevesii. We then compared the transcriptome profiles for this turtle species during the TSP with that for the American alligator Alligator mississippiensis to identify conserved reptilian TSD-related genes. Our transcriptome-based findings provide an opportunity to retrieve the candidate molecular cues that are activated during TSP and compare these target responses between TSD and GSD turtle species, and between TSD species.


Habitat availability drives the distribution-abundance relationship in phytophagous true bugs in managed grasslands.
The nearly universal positive relationship between the distribution and abundance of species has been explained by several hypotheses but hitherto no consensus has been reached. Here, we used monitoring data of 105 phytophagous true bug species (Heteroptera) from 150 grassland sites over six years to test how (1) range position, (2) resource use, (3) resource availability, (4) density-dependent habitat selection, (5) metapopulation dynamics, and (6) habitat dispersal affect the distribution-abundance relationship. For the use in a confirmatory path analysis, we constructed causal pathways representing the hypothesized relationships and tested them separately and in a combined analysis. Our results show that the distribution-abundance relationship in phytophagous true bugs is driven by habitat-availability. An increasing local density of the host-plants increases the distribution of the species in the landscape, which in turn increases their local abundance. Thereby habitat availability facilitates dispersal success. We conclude that local abundance of herbivores facing habitat destruction could decline owing to a decrease in population dynamics between sites at the landscape scale. Finally, our results underline the potential of confirmatory path analysis for testing competing hypotheses.


Frequent genomic loss at chr16p13.2 is associated with poor prognosis in colorectal cancer.
Genomic alterations play important roles in colorectal cancer (CRC) carcinogenesis. Here, we aimed to identify and characterize recurrent copy-number alterations (CNAs) associated with clinical outcome of CRC by the use of single nucleotide polymorphism arrays, genomic quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH). Colorectal neoplasia specimens and paired germline samples from 144 patients (40 adenomas and 104 carcinomas) as well as 40 CRC cell lines were investigated. This large dataset revealed frequent loss, including homozygous loss, at chr16p13.2 (from 5.9 to 7.42Mb). The loss was observed in 30% of adenomas and even more frequently in carcinomas, 56%, indicating that the loss define a subset of adenomas with a propensity for invasion. Consistent with this, the loss occurred twice as frequent in villous (40%) as in tubular adenomas (20%). The loss occurred independently of microsatellite stability and could be validated by qPCR in an independent sample cohort (n = 71). In Stage II/III, microsatellite stable (MSS) CRC it was associated with poor recurrence free survival (hazard ratio 2.4; p = 0.02; Multivariate Cox regression analysis). No transcriptional consequences of the losses were observed, and the only gene, A2BP1, located in the region showed no mutations. Correlation with other CNAs was established for chr3p22 in carcinomas and chr20p (inverse) in adenomas. FISH documented the chr16p13.2 region to be involved in complex structural rearrangements that included translocation to chr3p22 in some cases. The findings indicate that structural rearrangements involving chr16p13.2 are very frequent in colorectal neoplasia, often lead to homozygous deletion, and are associated with poor clinical outcome.


Identification of miR‑30b as an oncogene in renal cell carcinoma.
microRNAs (miRs) have been investigated as a novel class of regulators of cellular processes, including proliferation, apoptosis and metabolism. In particular, miR‑30b has been demonstrated to be deregulated in certain types of cancer, including lung, colorectal and gastric cancer. Previous studies of miR‑30b in renal clear cell carcinoma demonstrated that the expression level of miR‑30b was associated with distant metastasis. However, the function of miR‑30b in renal cell carcinoma (RCC) remained to be elucidated. In the present study, the expression of miR‑30b in 31 paired RCC tissues from four cell lines (786‑O, 769‑P, ACHN and 293T) was detected by reverse transcription‑quantitative polymerase chain reaction. In addition, the effect of miR‑30b on cell proliferation in RCC cells was also determined using MTT and Cell Counting Kit‑8 assay analyses. Furthermore, the function of miR‑30b in cell migration and invasion was determined by wound scratch and Transwell assays. Flow cytometry was also performed to quantify the effect of miR‑30b on cell apoptosis. The results of the current study indicated that miR‑30b was upregulated in RCC tissues from affected cell lines when compared with adjacent normal tissues and a normal kidney cell line, which is different to the downregulation of miR‑30b as observed in other types of cancer. miR‑30b is associated with RCC cell proliferation, invasion, migration and apoptosis, which indicated that miR‑30b acts as an oncogene in RCC. To the best of our knowledge, the present study is the first to demonstrate the upregulation of miR‑30b in RCC tissues and describe miR‑30b as an oncogene in RCC in the regulation of cell proliferation, migration, invasion and apoptosis. Further studies will define the target gene of miR‑30b in RCC and investigate the potential role of miR‑30b as a biomarker for RCC.


Elimination of soluble 123I-labelled aggregates of human immunoglobulin G in humans; the effect of splenectomy.
To study the role of the spleen in the elimination of immune complexes we examined mononuclear phagocyte system function in eight healthy controls and eight splenectomized patients, with soluble 123I-labelled aggregates of human immunoglobulin G (AIgG). No differences were found between the two groups in elimination and degradation of AIgG. The loss of splenic function was compensated for by increased uptake of AIgG by the liver. With the dose of 123I-AIgG used in this study (10 micrograms/kg body weight), significant generation of C3a was observed. No correlation was found between erythrocyte CR1 number and the fraction of aggregates that bound to erythrocytes.


Diversity of mitochondrial plastid DNAs (MTPTs) in seed plants.
Mitochondrial plastid DNAs (MTPTs) refer to plastid-derived DNA fragments in mitochondrial genomes. While the MTPTs have been described for numerous species, its overall patterns have not been examined in details. Here, we carried out a systematic analysis of MTPTs among 73 plant species, including 28 algae, 1 liverwort, 2 moss, 1 lycophyte, 1 gymnosperm, 1 magnoliid, 12 monocots, 26 eudicots and 1 relic angiosperm Amborella trichopoda. A total of 300 MTPT gene clusters were found in 39 seed plants, which represented 144 MTPT gene cluster types. The detected MTPT gene clusters were evaluated in seven aspects, and they were found to be enriched particularly in monocots and asterids of eudicots. Some MTPT gene clusters were found to be shared by closely related species. All chloroplast genes were found in MTPTs, suggesting that there is no functional relevancy for genes that were transferred. However, after calculation of the frequency of the 115 chloroplast genes, five hot spots and three cold spots were discovered in chloroplast genome. In summary, this study demonstrated the high degree of diversity in MTPTs. The discovered MTPTs would facilitate the accurate assembly of chloroplast and mitochondrial genomes as well as the understanding of organelle genome evolution.


PCR detection and analysis of the free-living amoeba Naegleria in hot springs in Yellowstone and Grand Teton National Parks.
Free-living thermotolerant amoebae pose a significant health risk to people who soak and swim in habitats suitable for their growth, such as hot springs. In this survey of 23 different hot springs in Yellowstone and Grand Teton National Parks, we used PCR with primer sets specific for Naegleria to detect three sequence types that represent species not previously described, as well as a fourth sequence type identified as the pathogen Naegleria fowleri.


Poor outcomes of delirium in the intensive care units are amplified by increasing age: A retrospective cohort study.
Delirium in patients in intensive care units (ICUs) is an acute disturbance and fluctuation of cognition and consciousness. Though increasing age has been found to be related to ICU delirium, there is limited evidence of the effect of age on delirium outcomes. The aim of this study is to investigate the relationship between age categories and outcomes among ICU delirium patients. Data were extracted from the electronic ICU (eICU) Collaborative Research Database with records from 3,931 patients with delirium. Patients were classified into non-aged (<65 years), young-old (65-74 years), middle-old (75-84 years), and very-old (≥85 years) groups. A Cox regression model was built to examine the role of age in death in ICU and in hospital after controlling covariates. The sample included 1,667 (42.4%) non-aged, 891 (22.7%) young-old, 848 (21.6%) middle-old, and 525 (13.3%) very-old patients. The ICU mortality rate was 8.3% and the hospital mortality rate was 15.4%. Compared with the non-aged group, the elderly patients (≥65 yeras) had higher mortality at ICU discharge (χ2 =13.726, P=0.001) and hospital discharge (χ 2=56.347, P<0.001). The Cox regression analysis showed that age was an independent risk factor for death at ICU discharge (hazard ratio [HR]=1.502, 1.675, 1.840, 95% confidence interval [CI] 1.138-1.983, 1.250-2.244, 1.260-2.687; P=0.004, 0.001, 0.002 for the young-, middle- and very-old group, respectively) as well as death at hospital discharge (HR=1.801, 2.036, 2.642, 95% CI 1.454-2.230, 1.638-2.530, 2.047-3.409; all P<0.001). The risks of death in the ICU and hospital increase with age among delirious patients.


Importance of primer selection in the application of PCR technology to the diagnosis of bovine leukemia virus.
The polymerase chain reaction (PCR) was used to detect bovine leukemia virus in bovine blood samples. When applied to leucocytes extracted from the blood samples, the standard method of DNA extraction gave good correlation with agar gel immunodiffusion, but a method in which 5 microliters of blood was the starting material was unreliable. Selection of the primers was important, and differences in results were observed when the PCR method was applied to blood samples from different geographic areas. The sensitivity varied from 50% to 90%, depending on the primer set applied to the gag gene of proviral nucleic acid. This variation was based on geographic origin of the cattle, suggesting an influence of viral strain. In some areas, more than 1 primer may needed to optimize results.


Erythropoietin to prevent and treat the anemia of prematurity.
Human recombinant erythropoietin was first cloned in 1985, and is currently available for clinical use for a variety of anemias. Following successful clinical trials using erythropoietin to treat adults with the anemia of end-stage renal disease, the first clinical trial evaluating the use of erythropoietin in preterm infants to treat anemia was published in 1990. Since that initial report, numerous clinical trials have reported various levels of success in the treatment of this anemia. Most recently, erythropoietin has been used in the first weeks of life in an attempt to prevent the anemia of prematurity. This review describes mechanisms of erythropoiesis in the fetus and neonate, and focuses on recent clinical trials evaluating the use of erythropoietin to prevent and treat anemia in preterm infants.


Artificial intelligence in spine care: current applications and future utility.
The field of artificial intelligence is ever growing and the applications of machine learning in spine care are continuously advancing. Given the advent of the intelligence-based spine care model, understanding the evolution of computation as it applies to diagnosis, treatment, and adverse event prediction is of great importance. Therefore, the current review sought to synthesize findings from the literature at the interface of artificial intelligence and spine research. A narrative review was performed based on the literature of three databases (MEDLINE, CINAHL, and Scopus) from January 2015 to March 2021 that examined historical and recent advancements in the understanding of artificial intelligence and machine learning in spine research. Studies were appraised for their role in, or description of, advancements within image recognition and predictive modeling for spinal research. Only English articles that fulfilled inclusion criteria were ultimately incorporated in this review. This review briefly summarizes the history and applications of artificial intelligence and machine learning in spine. Three basic machine learning training paradigms: supervised learning, unsupervised learning, and reinforced learning are also discussed. Artificial intelligence and machine learning have been utilized in almost every facet of spine ranging from localization and segmentation techniques in spinal imaging to pathology specific algorithms which include but not limited to; preoperative risk assessment of postoperative complications, screening algorithms for patients at risk of osteoporosis and clustering analysis to identify subgroups within adolescent idiopathic scoliosis. The future of artificial intelligence and machine learning in spine surgery is also discussed with focusing on novel algorithms, data collection techniques and increased utilization of automated systems. Improvements to modern-day computing and accessibility to various imaging modalities allow for innovative discoveries that may arise, for example, from management. Given the imminent future of AI in spine surgery, it is of great importance that practitioners continue to inform themselves regarding AI, its goals, use, and progression. In the future, it will be critical for the spine specialist to be able to discern the utility of novel AI research, particularly as it continues to pervade facets of everyday spine surgery.


Consumer interest in specialty beers in three European markets.
This study explores the quality perception of specialty beers (SBs) in Italy, Spain and Poland. Five-hundred and fifty mainstream beer consumers were enrolled in this study (two-hundred and thirty Italians, one hundred and sixty Poles and Spaniards respectively). The authors adopted a conjoint rating experiment in which the respondents were given forty SB profiles to evaluate. Each profile was described on six attributes (malt type, adjuncts, alternative source of sugars, characterizing ingredients, sensory characteristics, and retail price) varied at different levels and were asked to state his/her preference for each profile on a 9-point scale of interest. The results of this study showed that the ideal SB: (1) for the aggregate Polish panel is brewed from malted wheat, raw wheat, honey, and tropical fruits, is alcoholic and is priced below 2.00 Euros; (2) for the aggregate Italian panel consists of a beer brewed from malted wheat, maize, honey, and vanilla, is blonde and costs a maximum of 2.00 Euros; (3) for the aggregate Spanish panel is brewed from malted wheat, rye or maize, vanilla, is fruity and is priced below 2.00 Euros. The heterogeneity of interest in specialty beers observed in the three countries under test requires for the adaptation of a SB specifically to each culture in which it is sold. In this process of customization, brewers must take into account that gender modulates the effect of culture on consumer interest in SB sensory characteristics and ingredient formulation.


Which factors influence women in the decision to breastfeed?
Identify the factors that influence women in the decision to breastfeed. Integrative review. Information was gathered from original articles, case studies, theoretical studies, consensus and systematic reviews published between 2007-2013 in Spanish, Portuguese and English and recovered in the databases MEDLINE and LILACS. The descriptors used in this study were: breastfeeding, maternal behavior, risk factors, lactation and newborn. Were included 30 articles, grouped into five categories. Factors influencing the decision of the breastfeeding woman are a convergence of breastfeeding's advantages, benefits and justifications, family, social and professional support, sociodemographic and clinical characteristics of women, personal experience and family tradition and personal choice. The decision to breastfeed by women is influenced by a convergence of factors. It is essential the role of nursing to encourage women in the decision to initiate and maintain breastfeeding her child.


Value of Machine Learning with Multiphases CE-MRI Radiomics for Early Prediction of Pathological Complete Response to Neoadjuvant Therapy in HER2-Positive Invasive Breast Cancer.
To assess the value of radiomics based on multiphases contrast-enhanced magnetic resonance imaging (CE-MRI) for early prediction of pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients with human epithelial growth factor receptor 2 (HER2) positive invasive breast cancer. A total of 127 patients with newly diagnosed primary HER2 positive invasive breast cancer underwent CE-MRI before NAT and performed surgery after NAT. Radiomic features were extracted from the 1st postcontrast CE-MRI phase (CE1) and multi-phases CE-MRI (CEm),respectively. With selected features using a forward stepwise regression, 23 machine learning classifiers based on CE1 and CEm were constructed respectively for differentiating pCR and non-pCR patients. The performances of classifiers were assessed and compared by their accuracy, sensitivity, specificity and AUC (area under curve). The optimal machine learning classification was used to discriminate pCR vs non-pCR in mass and non-mass groups, uni-focal and unilateral multi-focal groups, respectively. For the task of pCR classification, 6 radiomic features from CE1 and 6 from CEm were selected for the construction of machine learning models, respectively. The linear SVM based on CEm outperformed the logistic regression model using CE1 with an AUC of 0.84 versus 0.69. In mass and non-mass enhancement groups, the accuracy of linear SVM achieved 84% and 76%. Whereas in unifocal and unilateral multifocal cases, 79% and 75% accuracy were achieved by linear SVM. Multiphases CE-MRI imaging may offer more heterogeneity information in the tumor and provide a non-invasive approach for early prediction of pCR to NAT in patients with HER2-positive invasive breast cancer.


Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.
Selective decontamination of the digestive tract (SDD) is an infection-prevention regimen used in critically ill patients. We assessed the effects of SDD on intensive-care-unit (ICU) and hospital mortality, and on the acquisition of resistant bacteria in adult patients admitted to intensive care. We did a prospective, controlled, randomised, unblinded clinical trial. 934 patients admitted to a surgical and medical ICU were randomly assigned oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime (SDD group n=466), or standard treatment (controls n=468). Primary endpoints were ICU and hospital mortality and the acquisition of resistant bacteria. In the SDD group 69 (15%) patients died in the ICU compared with 107 (23%) in the control group (p=0.002). Hospital mortality was lower in the SDD groups than in the control group (113 [24%] vs 146 [31%], p=0.02). During their stay in intensive care, colonisation with gram-negative bacteria resistant to ceftazidime, ciprofloxacin, imipenem, polymyxin E, or tobramycin occurred in 61 (16%) of 378 SDD patients and in 104 (26%) of 395 patients in the control group (p=0.001). Colonisation with vancomycin-resistant enterococcus occurred in five (1%) SDD patients and in four (1%) controls (p=1.0). No patient in either group was colonised with meticillin-resistant Staphylococcus aureus. In a setting with low prevalence of vancomycin-resistant enterococcus and meticillin-resistant S aureus, SDD can decrease ICU and hospital mortality and colonisation with resistant gram-negative aerobic bacteria.


Occlusion pressure and breathing pattern in children with chronic obstructive pulmonary disease.
The control of breathing at rest was studied in 30 children (3 to 17 years old) with chronic obstructive pulmonary disease (COPD). Five of them were tested several times during the follow-up of the COPD. Breathing pattern was evaluated and mouth occlusion pressure (PO.1) was measured. Results in COPD children were compared to previously reported values in healthy controls. PO.1 was significantly increased. In 11 children breathing O2, PO.1 decreased but remained at higher levels than predicted. However, the decrease in PO.1 in COPD was not significantly greater than in healthy children. These results may be explained by the relative mild hypoxemia in those children. The increase in PO.1 was significantly correlated with the increase in lung resistance (p less than 0.02) and with the decrease in dynamic lung compliance (p less than 0.01). Most of the COPD children were normocapnic. However, modifications in the breathing pattern were observed. The inspiratory time (TI) was significantly shortened, the expiratory time was prolonged and the TI over the total duration of the respiratory cycle was lowered. The respiratory frequency was unchanged. The tidal volume, normalized for body weight (VTBW), was increased. The mean inspiratory flow (VTBW/TI) was significantly augmented, but not as much as PO.1: in consequence, the effective inspiratory impedance was higher than predicted. Thus, as adults, COPD children had a greater inspiratory neural drive. In contrast to normocapnic COPD adults, they had a modified respiratory timing.


Vasculitis. A practical approach to management.
Vasculitis encompasses a wide variety of diseases. Because diagnosis may be difficult, a careful evaluation is essential, including a detailed patient history, thorough physical examination, and appropriate laboratory studies. Diagnosis is based on clinicopathologic features that permit identification of the condition. Biopsies are often necessary to confirm a diagnosis. It is important to accurately categorize the vasculitic disorders, since prompt, aggressive therapy with potentially toxic drugs is necessary to avoid irreversible organ system dysfunction.


Invasive pneumococcal disease a decade after pneumococcal conjugate vaccine use in an American Indian population at high risk for disease.
Before 7-valent pneumococcal conjugate vaccine (PCV7) introduction, invasive pneumococcal disease (IPD) rates among Navajo were several-fold those of the general US population. Only 50% of IPD cases in children involved PCV7 serotypes. We conducted active, population-based surveillance for IPD for the period 1995-2006. We documented case characteristics and serotyped the isolates. Over 12-year period, we identified 1508 IPD cases, 447 of which occurred in children aged <5 years. Rates of IPD due to vaccine serotypes among children aged <1 year, 1 to <2 years, and 2 to <5 years decreased from 210, 263, and 51 cases per 100,000 population, respectively in 1995-1997 to 0 cases in 2004-2006 (P < .001). Among adults aged > or =65 years, rates of IPD due to vaccine serotypes decreased 81% (95% confidence interval, -98% to -9%; P = .02). Rates of nonvaccine serotype IPD were unchanged in all age strata except for persons aged 18 to <40 years, among whom the rate decreased by 35% from 27 to 18 cases per 100,000 population (95% confidence interval, -57% to -1%; P = .03). Vaccine-serotype IPD has virtually been eliminated in the PCV7 era among Navajo of all ages. Overall rates of nonvaccine-serotype IPD have not increased, although increases have occurred for some individual types. Rates of all-serotype IPD among Navajo children remain 3-5-fold greater than in the general US population.


Efficacy of group biofeedback treatment on hyperemesis gravidarum with psychosomatic symptoms diagnosed with the revised version of Diagnostic Criteria for Psychosomatic Research (DCPR-R): study protocol for a randomised controlled trial.
Hyperemesis gravidarum (HG) is a condition characterised by dehydration, electrolyte imbalance, lack of nutrition and at least 5% loss in body weight, occurring in the first half of pregnancy. The aim of this trial is to examine the efficacy of group biofeedback treatment on patients with HG with psychosomatic symptoms, which will be evaluated through the revised version of Diagnostic Criteria for Psychosomatic Research (DCPR-R). In this single-blinded randomised controlled clinical trial, 68 patients with HG diagnosed with at least one psychosomatic syndrome according to DCPR-R and aged 18-40 years, will be recruited in a Chinese Maternal and Child Health Hospital. The sample will be randomised (1:1) into two arms: experimental group, which will undergo group biofeedback treatment, psycho-education and treatment as usual (TAU); and control group, which will undergo psycho-education and TAU only. The primary outcomes will be reduction of the frequency of psychosomatic syndromes, severity of nausea/vomiting, quality of life and heart rate variability. The secondary outcomes will include days of hospitalisation, repeated hospitalisation and laboratory investigations. This study has received ethical approval from the Nanjing Medical University (No. 2019/491, granted 22 February 2019). All participants will be required to provide written informed consent. Study outcomes will be disseminated through peer-reviewed publications and academic conferences, and used to confirm a tailored biofeedback intervention for patients with HG with psychosomatic symptoms. Chinese Clinical Trial Registry (ChiCTR2000028754).


Pelvic fractures: diagnostic and therapeutic angiography.
Pelvic ring disruption is part of a complex wounding pattern that challenges our ability to diagnose and manage hemorrhage. The conventional methods of diagnosis and control of abdominopelvic bleeding--peritoneal lavage and exploratory laparotomy--should be replaced by exploratory abdominopelvic angiography and transcatheter embolization. Angiography should be performed as soon as possible after the patient is admitted to the emergency room, and shock should not delay transfer of the patient to the angiography suite.


Global physiological analysis of carbon- and energy-limited growing Escherichia coli confirms a high degree of catabolic flexibility and preparedness for mixed substrate utilization.
Growth conditions for heterotrophic bacteria in the environment are characterized by low concentrations of carbon and energy sources and complex substrate mixtures. While mechanisms of starvation-survival in the absence of carbon substrates have been studied in considerable detail, information on the physiology of slow growth under oligotrophic conditions is limited. We intended to elucidate general strategies by which Escherichia coli adapts to low concentrations of a mixed carbon and energy source pool. A new screening method based on BIOLOG AN MicroPlates, which allowed us to distinguish repressed and induced catabolic functions in E. coli, was combined with the analysis of periplasmic high-affinity binding proteins. Extending previous findings for E. coli and other microbial species, we found that numerous alternative catabolic functions and high-affinity binding proteins are derepressed under either glucose- or arabinose-limited growth conditions, in spite of the absence of the respective inducers. Escherichia coli cells growing in carbon-limited complex medium chemostat cultures exhibited an even higher degree of catabolic flexibility and were able to oxidize 43 substrates. The BIOLOG respiration pattern indicated simultaneous dissimilation of diverse sugars, amino acids and dipeptides (mixed substrate growth). The observed physiological adaptations of E. coli to low concentrations of carbon and energy substrates presumably are advantageous in many natural growth situations and also offer an explanation why many heterotrophic bacteria have and maintain such a broad carbon substrate range.


Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein level predicts recurrence of hepatitis B virus-related hepatocellular carcinoma after curative resection.
To investigate whether serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) can predict the recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. Patients with chronic hepatitis B (CHB) who underwent curative resection for HCC between 2004 and 2015 were eligible for the study. Recurrence was sub-classified as early (<2 years) or late (≥2 years). A total of 170 patients with CHB were selected. During the follow-up period (median, 22.6 months), 64 (37.6%) patients developed recurrence. In multivariate analyses, WFA+-M2BP level was an independent predictor of overall (hazard ratio [HR]=1.490), early (HR=1.667), and late recurrence (HR=1.416), together with male sex, des-gamma carboxyprothrombin level, maximal tumor size, portal vein invasion, and satellite nodules (all P<0.05). However, WFA+- M2BP level was not predictive of grade B-C posthepatectomy liver failure. The cutoff value that maximized the sum of sensitivity (30.2%) and specificity (90.6%) was 2.14 (area under receiver operating characteristic curve=0.632, P=0.010). Patients with a WFA+-M2BP level >2.14 experienced recurrence more frequently than those with a WFA+-M2BP level ≤2.14 (P=0.011 by log-rank test), and had poorer postoperative outcomes than those with a WFA+-M2BP level ≤2.14 in terms of overall recurrence (56.0 vs. 34.5%, P=0.047) and early recurrence (52.0 vs. 20.7%, P=0.001). WFA+-M2BP level is an independent predictive factor of HBV-related HCC recurrence after curative resection. Further studies should investigate incorporation of WFA+-M2BP level into tailored postoperative surveillance strategies for patients with CHB.


Proximal junctional kyphosis in adult spinal deformity with long spinal fusion from T9/T10 to the ilium.
Proximal junctional kyphosis (PJK) is a common complication after corrective long spinal fusion for adult spinal deformity. Although some reports evaluated PJK after corrective long spinal fusion, there is no report about analysis of PJK cases in the same fusion area. The purpose of this study to investigated the incidence of and risk factors for PJK in adults undergoing long spinal fusion from the distal thoracic vertebrae (T9/T10) to the ilium. We enrolled 56 adult patients (>40 years of age) who underwent posterior corrective surgery with same fusion area from T9 or T10 to the ilium for spinal deformity. Pre- and postoperative radiographic measurements included the sagittal vertical axis (SVA), lumbar lordosis (LL), thoracic kyphosis (TK), pelvic tilt (PT), and pelvic incidence minus LL (PI-LL). The Oswestry disability index (ODI) was used to evaluate patient outcomes preoperatively and one year after surgery. We analyzed the incidence for PJK and compared PJK and non-PJK cases. PJK at the final follow-up occurred in 19 of 56 (33.9%) patients. The mean age and ODI were not significantly different between the PJK and non-PJK groups. Both two groups had good spinopelvic sagittal alignment after surgery in terms of SVA and PI-LL. Only three cases required revision surgery for symptomatic PJK. Three cases had history of rheumatoid arthritis and/or total hip arthroplasty surgery. The incidence of PJK was 33.9%, and ODI was not significantly different between the PJK and non-PJK groups. Symptomatic PJK was only three cases and all of them had lower extremity joint disorders. We should pay attention also lower extremity joint to prevent symptomatic PJK at the lower thoracic level.


Phase stability of colloidal mixtures of spheres and rods.
We determined the phase boundaries of aqueous mixtures containing colloidal rod-like fd-viruses and polystyrene spheres using diffusing-wave spectroscopy and compared the results with free volume theory predictions. Excluded volume interactions in mixtures of colloidal rods and spheres lead to mediated depletion interactions. The strength and range of this attractive interaction depend on the concentrations of the particles, the length L and diameter D of the rods, and the radius R of the spheres. At strong enough attraction, this depletion interaction leads to phase separation. We experimentally determined the rod and sphere concentrations where these phase transitions occur by systematically varying the size ratios L/R and D/R and the aspect ratio L/D. This was done by using spheres with different radii and modifying the effective diameter of the rods through either the ionic strength of the buffer or anchoring a polymeric brush to the surface of the rods. The observed phase transitions were from a binary fluid to a colloidal gas/liquid phase coexistence that occurred already at very low concentrations due to the depletion efficiency of highly anisotropic rods. The experimentally measured phase transitions were compared to phase boundaries obtained using free volume theory (FVT), a well established theory for calculating the phase behavior of colloidal particles mixed with depletants. We find good correspondence between the experimental phase transitions and the theoretical FVT model where the excluded volume of the rod-like depletants was explicitly accounted for in both the reservoir and the system.


Urolithiasis associated with experimental lymphocytic choriomeningitis virus inoculation in Lewis rats.
A high frequency of struvite urolithiasis, hydronephrosis, and other urinary tract lesions developed in a group of Lewis rats inoculated intracranially with lymphocytic choriomeningitis virus (LCMV). Initially, clinically ill rats were referred to necropsy: 30 rats over 3 years. These rats had high frequency of urolithiasis (8/30, 27%), hydronephrosis (12/30, 40%), cystitis (9/30, 30%), transitional cell carcinoma (4/30, 13%), and pyelonephritis (19/30, 63%). Lesions were more common in LCMV-inoculated rats. After this trend was noted, all rats on this protocol were necropsied as part of a cohort study (n = 144). Although the apparent frequency of disease was lower due to increased sampling, there still was a high number of urolithiasis (9/144, 6%) and hydronephrosis (40/144, 28%) cases. All cases of urolithiasis developed in rats inoculated with LCMV (9/44, 20%), as did most cases of hydronephrosis (31/44, 70%). Although sham-injected and uninoculated control rats also had high frequency of hydronephrosis (6/57 [11%] and 3/43 [7%], respectively), LCMV-inoculated rats had a significantly higher frequency of disease than did sham inoculated (P < 0.0001) and uninoculated (P < 0.0001) controls. These results suggest that Lewis rats may be predisposed to developing lesions of the urinary tract, and that intracranial inoculation of rats with LCMV augments this tendency, leading to formation of struvite calculi and associated urinary tract disease.


Rhodococcus equi pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature.
Rhodococcus equi is a cause of lung infection in immunosuppressed hosts. Since the start of the HIV epidemic, 76 cases of R. equi lung infection (MEDLINE 1985-96) affecting this population have been described. We report 2 additional cases and review the clinical data, radiological findings, treatment and outcome of these 78 patients. The mean age of these patients was 33 y; 69 were male. 71 met the criteria for AIDS (CDC 1993). Fever and cough were the presenting complaints in the majority of patients (84.3%). A single cavitary lung lesion in the upper lobes was the most common radiological finding (57.7%), although multiple cavitations, alveolar infiltrates and pleural effusion were also found. Treatment usually was based on synergistic antibiotic combinations for a long period of time determined on an individual basis. Surgery was performed only in 11 patients. Death attributable directly to R. equi infection is low (15.4%), however only half of the patients (53.8%) were completely cured. We conclude that R. equi infection should be strongly considered in any HIV patient who presents with cavitary lesions in the lung, especially if mycobacteria are not identified. Treatment must be based on synergistic antibiotic combinations, and surgery relegated to cases of chronic single cavitary lesions not responding to antibiotics.


Unraveling exercise addiction: the role of narcissism and self-esteem.
The aim of this study was to assess the risk of exercise addiction (EA) in fitness clubs and to identify possible factors in the development of the disorder. The Exercise Addiction Inventory (EAI), the Narcissistic Personality Inventory (NPI), and the Coopersmith Self-Esteem Inventory (SEI) were administered to a sample of 150 consecutive gym attenders recruited in fitness centers. Based on EAI total score, high EA risk group (HEA n = 51) and a low EA risk group (LEA n = 69) were identified. HEA reported significantly higher total score (mean = 20.2 versus 14.6) on the NPI scale and lower total score (mean = 32.2 versus 36.4) on the SEI scale than LEA. A stepwise regression analysis indicated that only narcissism and self-esteem total scores (F = 5.66; df = 2; P = 0.006) were good predictors of days per week exercise. The present study confirms the direct and combined role of both labile self-esteem and high narcissism in the development of exercise addiction as predictive factors towards the risk of addiction. Multidisciplinary trained health care providers (physiatrists, psychologists, and psychiatrists) should carefully identify potential overexercise conditions in order to prevent the potential risk of exercise addiction.


Prevalence and determinants of cervical cancer screening: a community-based study in Singapore.
A cross-sectional survey of 568 married women aged 21-65 years in the Pasir Panjang Constituency was conducted to determine the prevalence of cervical cancer screening in the community and the factors affecting acceptance of this screening test. Results show that 309 (54.4%) of the respondents had ever had a Pap smear. The women who reported having had a smear were more likely to be below 45 years of age (prevalence ratio 1.47, 95% confidence interval 1.15 to 1.88), Chinese and of a higher socioeconomic status (1.68, 1.33 to 2.12). They were also more likely to have married at a later age (1.68, 1.21 to 2.31) than women who had not had a smear. Age and socioeconomic status remained independent predictors on multivariate analysis. The findings suggest that an important task of public health practitioners is to increase the uptake of screening among older and socially disadvantaged women who are known to be at the highest risk of cervical cancer. In addition, strategies to encourage younger women to continue regular attendance at screening clinics beyond their childbearing years will be important for the future.


Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort.
With the use of potent antiretroviral therapy in patients with HIV disease, changes in lipid parameters and glucose homeostasis have been noted. However, these effects have been difficult to interpret because of the varied demographic and treatment characteristics of the cohorts and the complexity of differentiating the effect of HIV disease from that of the drugs used in its treatment. This study was designed to explore these issues. Demographic information and fasting blood samples were collected from 419 antiretroviral-naive HIV-1-infected patients. The average age of the participants was 38.2 years, with 21% being female, 60% being African American, and 14% having a history of injection drug use. The mean CD4 lymphocyte count was 216 cells/microL, the mean baseline log10 HIV viral load was 4.98 HIV-1 RNA copies/mL, and 26% of patients had a history of AIDS-defining events. Women and African Americans had significantly higher levels of high-density lipoprotein (HDL) cholesterol, and older age was associated with higher total cholesterol levels. Lower CD4 lymphocyte counts and higher HIV RNA levels were independently associated with lower HDL cholesterol levels. Additionally, higher HIV RNA level was associated with lower levels of low-density lipoprotein (LDL) cholesterol and higher levels of very-low-density lipoprotein (VLDL) cholesterol and triglycerides. A history of AIDS-defining events was associated with higher total cholesterol, VLDL cholesterol and triglyceride concentrations. With respect to glucose homeostasis, a higher CD4 lymphocyte count was associated with less evidence of insulin resistance. However, a higher body mass index was associated with higher lipid levels and with more evidence of insulin resistance. Both HIV disease and demographic characteristics were found to influence lipid values and glucose homeostasis in the absence of antiretroviral treatment. More advanced HIV disease was associated with less favourable lipid and glucose homeostatic profiles. The independent association between HIV RNA levels and various lipid parameters suggests that viral replication had a direct effect on lipid levels. Interpretation of the effects of various HIV treatment regimen and drugs on metabolic parameters must take into account the stage of HIV disease and the demographic characteristics of the population studied.


[Discussion on theoretical history of Jingluo: a review of Thousands of Years Innovations of Jingluo: Theoretical and Clinical Thinkings Through the Ages by ZHANG Jian-bin].
The author reviewed the book of Thousands of Years Innovations of Jingluo: Theoretical and Clinical Thinkings Through the Ages by ZHANG Jian-bin, and put forth some evaluations, believing that the book has 4 extraordinary perspectives, clear definition for Jingluo theory, clinical thinking angle, zangfu-jingluo integrating narrative, and discipline structure maintaining. In addition, the values, trends andmethods of Jingluo theory research were also proposed in this book review.


Initial experience with the TightRail™ Rotating Mechanical Dilator Sheath for transvenous lead extraction.
In parallel with increasing implantation rates and patients' longer life expectancy, the need for transvenous lead extraction (TLE) as a specialized procedure has shown a significant growth over years. Herein, we aimed to present our initial experience in TLE by using a novel TightRail™ Rotating Mechanical Dilator Sheath. Between October 2014 and March 2015, a total of 42 leads in 23 patients were removed at our tertiary referral centre. All of the extracted leads were >12 months old and indications for extraction were based on the recommendations of the Heart Rhythm Society. The leads were removed by using the TightRail™ Mechanical Dilator Sheath (Spectranetics Corporation) with the rotational cutting force only. Indications for lead removal included cardiac device infection in 12 (52.2%) cases, lead malfunction in the 10 (43.5%) cases, and upgrade to cardiac resynchronization therapy-defibrillator (CRT-D) in the remaining 1 case (4.3%). The extracted devices were pacemaker in 10 (43.4%) cases, implantable cardioverter-defibrillator (ICD) in 7 (30.4%) cases, and CRT in the remaining 6 (26.0%) subjects. Among 42 leads, 10 (23.8%) were right ventricular, 14 (33.3%) were atrial, 13 (31.0%) were defibrilator, and 5 (11.9%) were coronary sinus electrodes. The median time from implantation was 72 (18-216) months. Complete procedural success with TightRail™ system alone was achieved in 22 (95.7%) patients (41/42 leads) and overall clinical success was 100%. One right ventricular lead was completely removed with the help of femoral snare. All the patients were discharged uneventfully without any complication. Our preliminary data with small sample size show that TightRail™ Mechanical Dilator Sheath is a new useful tool for chronically implanted pacemaker (PM)/ICD leads. Continued investigation including large patient cohort is required to evaluate success and complication rates in comparison to other tools and techniques.


Paper card-like electrochemical platform as a smart point-of-care device for reagent-free glucose measurement in tears.
This communication describes the development of polyvinyl chloride electrochemical system in which a paper layer loaded with reagents is inserted into the device, demonstrating a new concept of a paper card-like pad for a reagent-free and easy measurement of the target analyte in solution. This device detects glucose in artificial tears in the range of 0.2-2 mM with a detection limit of 50 μM by simply adding the artificial tears to the paper card-like pad. The novel configuration goes beyond the state of the art, widening the application range of paper in the design of smart analytical devices.


Template-free synthesis of porous carbon from triazine based polymers and their use in iodine adsorption and CO2 capture.
A series of novel triazine-containing pore-tunable carbon materials (NT-POP@800-1-6), which was synthesized via pyrolysis of porous organic polymers (POPs) without any templates. NT-POP@800-1-6 possess moderate BET surface areas of 475-736 m2 g-1, have permanent porosity and plenty of nitrogen units in the skeletons as effective sorption sites, and display relatively rapid guest uptake of 56-192 wt% in iodine vapour in the first 4 h. In addition, all the samples exhibit the outstanding CO2 adsorption capacity of 2.83-3.96 mmol g-1 at 273 K and 1.05 bar. Furthermore, NT-POP@800-1-6 show good selectivity ratios of 21.2-36.9 and 3.3-7.5 for CO2/N2 or CH4/N2, respectively. We believe that our new building block design provides a general strategy for the construction of triazine-containing carbon materials from various extended building blocks, thereby greatly expanding the range of applicable molecules.


Nd(3+)-sensitized upconversion nanophosphors: efficient in vivo bioimaging probes with minimized heating effect.
Upconversion (UC) process in lanthanide-doped nanomaterials has attracted great research interest for its extensive biological applications in vitro and in vivo, benefiting from the high tissue penetration depth of near-infrared excitation light and low autofluorescence background. However, the 980 nm laser, typically used to trigger the Yb(3+)-sensitized UC process, is strongly absorbed by water in biological structures and could cause severe overheating effect. In this article, we report the extension of the UC excitation spectrum to shorter wavelengths, where water has lower absorption. This is realized by further introducing Nd(3+) as the sensitizer and by building a core/shell structure to ensure successive Nd(3+) → Yb(3+) → activator energy transfer. The efficacy of this Nd(3+)-sensitized UC process is demonstrated in in vivo imaging, and the results confirmed that the laser-induced local overheating effect is greatly minimized.


Active learning of enhancer and silencer regulatory grammar in photoreceptors.
Cis-regulatory elements (CREs) direct gene expression in health and disease, and models that can accurately predict their activities from DNA sequences are crucial for biomedicine. Deep learning represents one emerging strategy to model the regulatory grammar that relates CRE sequence to function. However, these models require training data on a scale that exceeds the number of CREs in the genome. We address this problem using active machine learning to iteratively train models on multiple rounds of synthetic DNA sequences assayed in live mammalian retinas. During each round of training the model actively selects sequence perturbations to assay, thereby efficiently generating informative training data. We iteratively trained a model that predicts the activities of sequences containing binding motifs for the photoreceptor transcription factor Cone-rod homeobox (CRX) using an order of magnitude less training data than current approaches. The model's internal confidence estimates of its predictions are reliable guides for designing sequences with high activity. The model correctly identified critical sequence differences between active and inactive sequences with nearly identical transcription factor binding sites, and revealed order and spacing preferences for combinations of motifs. Our results establish active learning as an effective method to train accurate deep learning models of cis-regulatory function after exhausting naturally occurring training examples in the genome.


Regulating Oxygen Vacancies and Fermi Level of Mesoporous CeO2-x for Intensified Built-In Electric Field and Boosted Charge Separation of Cs3 Bi2 Br9 /CeO2-x S-Scheme Heterojunction.
Regulating the built-in electric field (BEF) in the heterojunction is is a great challenge in developing high-efficiency photocatalysts. Herein, by tailoring the content of oxygen vacancies in the constituent reduction semiconductor (mesoporous CeO2-x ), a precise Fermi level (EF ) regulation of CeO2-x is realized, yielding an amplified EF gap and intensified BEF in the Cs3 Bi2 Br9 perovskite quantum dots/CeO2-x S-scheme heterojunction. Such an enhanced BEF offers a strong driving force for directional electron transfer, boosting charge separation in the S-scheme heterojunction. As a result, the optimized Cs3 Bi2 Br9 /CeO2-x heterojunction delivers a remarkable CO2 conversion efficiency, with an impressive CO production rate of 80.26 µmol g-1 h-1 and a high selectivity of 97.6%. The S-scheme charge transfer mode is corroborated comprehensively by density functional theory (DFT) calculations, in situ X-ray photoelectron spectroscopy (XPS), and photo-irradiated Kelvin probe force microscopy (KPFM). Moreover, diffuse reflectance infrared Fourier transform spectra (DRIFTS) and theoretical calculations are conducted cooperatively to reveal the CO2 photoreduction pathway.


[Atopy spectrum and its relationship with clinical characteristics in asthmatic children under 4 years of age].
To study the atopy spectrum and the influence of clinical characteristics upon it in asthmatic children under 4 years of age. Clinical data of 62 asthmatic children under 4 years of age, including age, sex, the age of first wheezing attack, the total times of wheezing attack, the duration of history of wheezing, and the allergic history of both children and parents, were collected. The screening tests on allergens (fx5E, mx2 and Phadiatop) were conducted by fluoroenzyme-immunometric assay using the UniCAP100 system. The total serum IgE level was also measured. Logistic regression was used to analyze the effect of clinical characteristics on allergic sensitization. The positive rates of fx5E, mx2 and Phadiatop were 40.3%, 14.5% and 14.5% respectively, and the total allergic sensitization screening test rate was 46.8%. The sensitization rate to inhalant allergens was 24.2%. The allergic history of parent (s), the sensitization to food allergens, the age of first wheezing attack and total serum IgE level were main factors influencing the sensitization to inhalant allergens. About a quarter of asthmatic children under 4 years of age showed sensitization to inhalant allergens. The asthmatic history of parent (s), the sensitization to food allergens, the age of first wheezing attack greater than 2 years and the significantly higher total serum IgE level may increase the possibility of sensitization to inhalant allergens in asthmatic children under 4 years of age.


Live Fluorescence, Inverse Imaging of Cell Ruffling, and Macropinocytosis.
Macropinocytosis is a highly conserved but still incompletely understood process that is essential for the uptake and ingestion of fluid, fluid-phase nutrients and other material in cells. The dramatic extension of cell surface ruffles, their closure to form macropinosomes, and the maturation of internalized macropinosomes are key events in this pathway that can be difficult to capture using conventional confocal imaging based on tracking a bolus of fluorescent cargo. Fluorescent dextrans are commonly used experimentally as fluid phase markers for macropinosomes and for other endocytic pathways. A method the lab has adopted to optimize the imaging of dextran uptake involves using live imaging of cells bathed in high concentrations of fluorescent dextran in the medium, with the unlabeled cells appearing in relief (as black). The cell ruffles are highlighted to visualize ruffle closure, and internalized macropinosomes appear as fluorescent vacuoles in the cell interior. This method is optimal for visualizing macropinosome features and allows for easy segmentation and quantification. This paper describes dual-labeling of pathways with different sized dextrans and the co-expression of lipid probes and fluorescent membrane proteins to demark macropinosomes and other endosomes. The detection of internalized dextran at an ultrastructural level using correlative light and electron microscopy (CLEM) is also demonstrated. These cell processes can be imaged using multiple live imaging modalities, including in 3D. Taken together, these approaches optimize macropinosome imaging for many different settings and experimental systems.


Electrostatic potential modulations on polynucleotides as a function of ionic content: potentiometric determinations.
pK values of ionisation of cytidine residues, in poly C and poly I. poly C, have been determined by potentiometric titration as a function of either ionic strength (Na+) or Mg2+ concentration. The results are interpreted as a consequence of the existence of a local pH, prevailing in the vicinity of the polynucleotides, smaller than that of the bulk solution. This local pH is dependent upon the electrostatic potential psi due to the negatively charged phosphate groups of the polynucleotide. Moreover psi can be modulated through variation of either ionic strength or Mg2+ concentration. At a given pH Mg2+ addition leads to the release of protons which, in the case of complex systems of limited stability, might be detected by the use of the pH-stat method. Possible functional implications for genetic translation systems are examined.


Multimorbidity and healthcare utilization among home care clients with dementia in Ontario, Canada: A retrospective analysis of a population-based cohort.
For community-dwelling older persons with dementia, the presence of multimorbidity can create complex clinical challenges for both individuals and their physicians, and can contribute to poor outcomes. We quantified the associations between level of multimorbidity (chronic disease burden) and risk of hospitalization and risk of emergency department (ED) visit in a home care cohort with dementia and explored the role of continuity of physician care (COC) in modifying these relationships. A retrospective cohort study using linked administrative and clinical data from Ontario, Canada, was conducted among 30,112 long-stay home care clients (mean age 83.0 ± 7.7 y) with dementia in 2012. Multivariable Fine-Gray regression models were used to determine associations between level of multimorbidity and 1-y risk of hospitalization and 1-y risk of ED visit, accounting for multiple competing risks (death and long-term care placement). Interaction terms were used to assess potential effect modification by COC. Multimorbidity was highly prevalent, with 35% (n = 10,568) of the cohort having five or more chronic conditions. In multivariable analyses, risk of hospitalization and risk of ED visit increased monotonically with level of multimorbidity: sub-hazards were 88% greater (sub-hazard ratio [sHR] = 1.88, 95% CI: 1.72-2.05, p < 0.001) and 63% greater (sHR = 1.63; 95% CI: 1.51-1.77, p < 0.001), respectively, among those with five or more conditions, relative to those with dementia alone or with dementia and one other condition. Low (versus high) COC was associated with an increased risk of both hospitalization and ED visit in age- and sex-adjusted analyses only (sHR = 1.11, 95% CI: 1.07-1.16, p < 0.001, for hospitalization; sHR = 1.07, 95% CI: 1.03-1.11, p = 0.001, for ED visit) but did not modify associations between multimorbidity and outcomes (Wald test for interaction, p = 0.566 for hospitalization and p = 0.637 for ED visit). The main limitations of this study include use of fixed (versus time-varying) covariates and focus on all-cause rather than cause-specific hospitalizations and ED visits, which could potentially inform interventions. Older adults with dementia and multimorbidity pose a particular challenge for health systems. Findings from this study highlight the need to reshape models of care for this complex population, and to further investigate health system and other factors that may modify patients' risk of health outcomes.


[Cephradine in open heart serugery. Concentrations of cephradine in pericardial exudate and serum after cardiac surgery (author's transl)].
The diffusion of cephradine into the pericardial exudate was measured in 19 patients undergoing heart surgery. Every patient received 2 grams of cephradine (=30 mg/kg) during a 20 minute infusion period, before, during, and after the operation, and than at intervals of 6 hours, together 8 grams per day. The highest mean serum level, 10 minutes after the end of the first injection was 150 microgram/ml and after repeated dosages 102.5 microgram/ml, and at the end of the infusion interval 3.2 microgram/ml in the mean. At the time of opening the pericardium the concentration of the substance in the pericardial exudate, 15, 30, 45 and 60 minutes after finishing the first injection, varied from 4.1 to 38.6 microgram/ml in the average. The postoperative maximum levels were higher than 50 microgram/ml and 6 hours after the respective administrations the levels varied between 12.83 and 15.77 microgram/ml in each case. These high concentrations of cephradine in the pericardial exudate could not be attributed to seepage of blood into the pericardium.-At specific "check points" bacteriological materials were taken. Out of 1168 specimens only 6.7% were bacteriological positive. Drains in wounds, the pleura or the pericardium were sterile in most cases. Intravenous catheters were contaminated only in 1%. However the contamination rate rises with period of storage. The results show that cephradine exhibits good diffusion into the exudate of pericardium. With the chosen dosage the concentrations of the antibiotic in the pericardial exudate are higher than the MIC values of most pathogen bacteria.


Factors affecting clinical outcomes in women with non-gastric gastrointestinal stromal tumors.
The clinical presentation of non-gastric GISTs might mimic adnexal cancer, and non-gastric GIST might be managed and treated by gynecologists. Knowledge of the clinical outcomes of women with non-gastric gastrointestinal stromal tumors (GISTs) is important. Our aim is to elucidate the factors affecting the clinical outcomes of women with non-gastric GISTs. Between January 2000 and October 2019, all consecutive women with non-gastric GISTs who underwent surgery in a tertiary referral center were reviewed. Twenty-six women were reviewed. Eight (31%) women experienced recurrence. The probabilities of recurrence-free survival (RFS) at 60 and 120 months were 65.2% and 55.9%, respectively. The probabilities of overall survival (OS) at 60 and 120 months were 71.1% and 63.9%, respectively. Cancer stage was the only independent predictor of RFS (hazard ratio = 6.00, p = 0.007) and OS (hazard ratio = 3.88, p = 0.04). However, excluding cancer stage, metastasis (hazard ratio = 8.74) was the only independent predictor of RFS, and tumor size (hazard ratio = 1.20) and metastasis (hazard ratio = 6.03) were independent predictors of OS. Tumor size ≥13.9 cm was the optimum cut-off value to predict death and had an area under the receiver operating characteristic curve of 0.75 (95% confidence interval = 0.53 to 0.98). Among the above 5 women with non-gastric GISTs admitted to the Gynecology Department, optimal debulking surgery was performed in two women, and small bowel resection was performed in three women; and all five women remained alive without disease. Non-gastric GISTs may mimic gynecologic tumors. Metastasis was an independent predictor of PFS. In addition, metastasis and large tumor size (especially ≥13.9 cm) were independent predictors of OS in women with non-gastric GISTs.


A Low-Power Wearable Stand-Alone Tongue Drive System for People With Severe Disabilities.
This paper presents a low-power stand-alone tongue drive system (sTDS) used for individuals with severe disabilities to potentially control their environment such as computer, smartphone, and wheelchair using their voluntary tongue movements. A low-power local processor is proposed, which can perform signal processing to convert raw magnetic sensor signals to user-defined commands, on the sTDS wearable headset, rather than sending all raw data out to a PC or smartphone. The proposed sTDS significantly reduces the transmitter power consumption and subsequently increases the battery life. Assuming the sTDS user issues one command every 20 ms, the proposed local processor reduces the data volume that needs to be wirelessly transmitted by a factor of 64, from 9.6 to 0.15 kb/s. The proposed processor consists of three main blocks: serial peripheral interface bus for receiving raw data from magnetic sensors, external magnetic interference attenuation to attenuate external magnetic field from the raw magnetic signal, and a machine learning classifier for command detection. A proof-of-concept prototype sTDS has been implemented with a low-power IGLOO-nano field programmable gate array (FPGA), bluetooth low energy, battery and magnetic sensors on a headset, and tested. At clock frequency of 20 MHz, the processor takes 6.6 s and consumes 27 nJ for detecting a command with a detection accuracy of 96.9%. To further reduce power consumption, an application-specified integrated circuit processor for the sTDS is implemented at the postlayout level in 65-nm CMOS technology with 1-V power supply, and it consumes 0.43 mW, which is 10 lower than FPGA power consumption and occupies an area of only 0.016 mm.


Parameters influencing potency of Bacillus thuringiensis var. israelensis products.
Bioassays of products based on Bacillus thuringiensis var. israelensis have been carried out according to standard protocols. These analyses revealed that the slopes of the log-probit transformed concentration mortality curves of various products were different from that of the international standards (IPS82 for B. thuringiensis israelensis). For statistical reasons, this invalidates the tests. Products giving various slopes of the concentration mortality curves will obtain different potencies when estimated at a LC90 level than when estimated at LC50 level, as normally done. The LC90 level is probably more relevant for the field effect. Changing the median particle size of a product in a non destructive way results in change of slope and LC50 and thereby potency. Therefore, potency of a product as measured in these bioassays is not just a measure of the quantity of B. thuringiensis israelensis crystal protein present, but a function of product parameters like median particle size. Biochemical methods for quantification of toxin can therefore not relate simply to potency of the products obtained with this method. It is suggested that standard protocols for bioassay may be changed to assure equal particle size of products and samples to obtain parallel dose response.


Postmortem sperm procurement.
We determined the prevalence of requests for postmortem sperm procurement and the degree to which procurement is performed by those working in the field of infertility. Structured telephone interviews were conducted with personnel at 273 assisted reproductive facilities in the United States and Canada. The number of facilities reporting requests and the number of facilities reporting that they performed the procedure were determined. The prevalence of requests for postmortem sperm procurement was much greater than initially anticipated. A total of 82 requests was reported at 40 facilities in 22 different states between 1980 and 1995. More than half of the reported requests (43) were made between 1994 and 1995. Of the 82 requests 25 were honored at 14 facilities in 11 different states. No requests or procedures were reported from Canada. Medical advances in postmortem sperm procurement, cryopreservation and in vitro fertilization permit retrieval of sperm after death for various purposes, including posthumous fatherhood. There are no explicit ethical guidelines, legislation or relevant case law, and fertility specialists must confront these issues before proceeding in a field fraught with moral and policy uncertainties.


An Introduction to the Blockchain and Its Implications for Libraries and Medicine.
The blockchain is a relatively new technology used to verify and store transaction records for online cryptocurrencies like Bitcoin. The system is redundant and distributed, making it difficult for transactions to be rescinded, duplicated, or faked. Beyond online currencies, the blockchain has potential uses in health care, education, and many other fields. This column will briefly describe what the blockchain is and how it is being used, potential future uses that may be of interest to librarians and medical practitioners, and some of the problems with the system.


Ghrelin and measures of satiety are altered in polycystic ovary syndrome but not differentially affected by diet composition.
Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age associated with obesity. It may involve dysregulation of ghrelin, a hormone implicated in appetite regulation. The effect of diet composition on ghrelin is unclear. Overweight women with and without PCOS were randomized to a high-protein (40% carbohydrate, 30% protein; 10 PCOS, six non-PCOS) or standard protein diet (55% carbohydrate, 15% protein; 10 PCOS, six non-PCOS) for 12 wk of energy restriction and 4 wk of weight maintenance. Diet composition had no effect on fasting or postprandial ghrelin or measures of satiety. Non-PCOS subjects had a 70% higher fasting baseline ghrelin (P = 0.011), greater increase in fasting ghrelin (57.5 vs. 34.0%, P = 0.033), and greater maximal decrease in postprandial ghrelin after weight loss (-144.1 +/- 58.4 vs. -28.9 +/- 14.2 pg/ml, P = 0.02) than subjects with PCOS. Subjects with PCOS were less satiated (P = 0.001) and more hungry (P = 0.007) after a test meal at wk 0 and 16 than subjects without PCOS. Appetite regulation, as measured by subjective short-term hunger and satiety and ghrelin homeostasis, may be impaired in PCOS.


Treatment modalities in brachioradial pruritis: a systematic review.
Brachioradial pruritis is a rare dysesthesia syndrome that is known to negatively impact quality of life. No consensus exists regarding optimal treatment strategies. We searched MEDLINE, EMBASE, and the Cochrane Collaboration Clinical Trials Registry from 1966 to 2021 for studies using the title word "brachioradial pruritis" with no language restriction. One author (A.Z.) screened and performed full article reviews of all randomized clinical trials, cohort studies, case-control studies, case reports, and case series describing treatment outcomes among patients with brachioradial pruritis. We identified 239 potential articles with a final set of 45 articles meeting inclusion criteria. Only a single randomized clinical trial was identified, finding no significant benefit of topical capsaicin cream. Treatment modalities with the greatest number of reported successful therapeutic trials include gabapentin and tricyclic antidepressants. In patients with confirmed cervical spine disease, spine-directed therapies such as epidural injections were found to be beneficial. Case reports and small case series describing less-common treatments were also identified. The literature is overall limited with the greatest support for gabapentin, pregabalin, tricyclic antidepressants, and spine-directed therapies in appropriate patients with brachioradial pruritis. Future randomized clinical trials are needed to compare the relative effectiveness of available treatments.


Dissecting comimetic radiations in Heliconius reveals divergent histories of convergent butterflies.
Mimicry among Heliconius butterflies provides a classic example of coevolution but unresolved relationships among mimetic subspecies have prevented examination of codiversification between species. We present amplified fragment length polymorphism and mtDNA datasets for the major comimetic races of Heliconius erato and H. melpomene. The AFLP data reveal unprecedented resolution, clustering samples by geography and race in both species. Our results show that, although H. erato and H. melpomene co-occur, mimic each other, and exhibit parallel shifts in color pattern, they experienced very different modes of diversification and geographic histories. Our results suggest that H. erato originated on the western side of South America whereas H. melpomene originated in the east. H. erato underwent rapid diversification and expansion with continued gene-flow following diversification, resulting in widely dispersed sister taxa. In contrast, H. melpomene underwent a slower pace of diversification with lower levels of gene flow, producing a stepwise directional expansion from west to east. Our results also suggest that each of the three main wing pattern phenotypes originated and/or was lost multiple times in each species. The rayed pattern is likely to be the ancestral phenotype in H. erato whereas postman or red patch is likely to be ancestral in H. melpomene. Finally, H. cydno and H. himera are monophyletic entities clearly nested within H. melpomene and H. erato, rather than being their respective sister species. Estimates of mtDNA divergence suggest a minimum age of 2.8 and 2.1 My for H. erato and H. melpomene, respectively, placing their origins in the late Pliocene.


Mixed metastatic lung cancer lesions in bone are inhibited by noggin overexpression and Rank:Fc administration.
Lung cancer metastases to bone produce a primarily mixed osteolytic/osteoblastic lesion. The purpose of this study was to determine if blockade of both pathways would inhibit the formation these lesions in bone. Inhibition of the osteoblastic lesion with noggin and the osteolytic lesion with RANK:Fc was a successful treatment strategy to inhibit progression of mixed lung cancer lesions in bone. Approximately 9-30% of patients with lung cancer develop bone metastases, leading to significant morbidity and mortality. A549 is a non-small-cell lung cancer (NSCLC) line that produces a mixed metastatic lesion in bone. We sought to determine if blockade of key components in both osteolytic and osteoblastic pathways would result in a reduction of a NSCLC tumor progression in a murine model of bony metastasis. The study used a retroviral vector overexpressing noggin (RN), a specific inhibitor of BMP, and RANK:Fc, a chimeric protein that inhibits the RANK-RANKL interaction. A549 cells were transduced with RN before implantation in SCID mice. Cells were implanted in a subcutaneous model and tibial injection model. RANK:Fc was administered twice weekly at 15 mg/kg. There were five treatment groups: A549; A549 + RN; A549 + RANK:Fc; A549 + empty vector; and A549 + RN + RANK:Fc (n = 10/group). In SCID mice who underwent subcutaneous A549 tumor cell injection, animals treated with A549 + RN had significantly smaller subcutaneous tumor size at 8 weeks. In an intratibial model of bony metastasis, animals injected with A549 cells developed a mixed lytic/blastic lesion with cortical destruction at 8 weeks. Treatment with RANK:Fc inhibited the formation of osteoclasts, led to a smaller tumor volume in bone, and inhibited the lytic component of the mixed lesion. Animals treated with A549 + RN had a decreased number of osteoblasts in bone lesions, smaller tumor volume, and inhibition of the blastic component of the mixed lesions. Combination treatment inhibited both the lytic and blastic components of the lesion. The NSCLC cell line A549 forms a mixed osteolytic/osteoblastic lesion in vivo. Noggin overexpression inhibited the formation of the osteoblastic aspect of the lesion in bone and the tumor growth in vivo. Treatment with RANK:Fc limited the formation of the lytic aspect of the mixed lesion and also inhibited the rate of in vivo tumor growth. Inhibition of both pathways is necessary to effectively inhibit the progression of mixed metastatic lesions in bone.


Analysis of web height ratios according to age and sex.
Each component of the web space, a three-dimensional structure, should be carefully created during reconstruction of web space loss. One of these web space components is the web height. In this study, the dorsal view of subjects' hands was analyzed to determine the web height ratios. The web height ratios were then compared with respect to age and sex. The second and third web height ratios differed between adult men and women and between children and adults. However, no differences were observed among children. This study is unique because it focuses on the web height ratios of all web spaces according to age and sex and provides a very easy-to-use scale that may help surgeons to perform web space reconstruction. Moreover, the present study adds to the literature by providing information on the first web height ratios of the hand.


Three-dimensional imaging of Poland's syndrome.
Use of a three-dimensional CT scan as an adjunct for planning chest-wall and breast reconstruction in Poland's syndrome is presented with follow-up MRI with three-dimensional reformation to demonstrate the results of the implant reconstruction. The imaging techniques are capable of accurately portraying the three-dimensional tissue deficit and asymmetry. This imaging may assist in the choice of muscle transposition flaps and reconstructive technique.


Mycobacterium tuberculosis-macrophage interaction: Molecular updates.
Mycobacterium tuberculosis (Mtb), the causative agent of Tuberculosis (TB), remains a pathogen of great interest on a global scale. This airborne pathogen affects the lungs, where it interacts with macrophages. Acidic pH, oxidative and nitrosative stressors, and food restrictions make the macrophage's internal milieu unfriendly to foreign bodies. Mtb subverts the host immune system and causes infection due to its genetic arsenal and secreted effector proteins. In vivo and in vitro research have examined Mtb-host macrophage interaction. This interaction is a crucial stage in Mtb infection because lung macrophages are the first immune cells Mtb encounters in the host. This review summarizes Mtb effectors that interact with macrophages. It also examines how macrophages control and eliminate Mtb and how Mtb manipulates macrophage defense mechanisms for its own survival. Understanding these mechanisms is crucial for TB prevention, diagnosis, and treatment.


Pulmonary edema as a complication of interleukin-2 therapy.
Eight patients underwent IV bolus therapy with recombinant interleukin-2 (Cetus Corporation, Emeryville, CA) for treatment of metastatic melanoma or renal cell carcinoma. The patients were randomized to receive interleukin-2 alone or interleukin-2 in combination with lymphokine-activated killer cells. Radiographs showed pulmonary edema in five of the eight patients. The changes ranged from mild interstitial edema (two patients) to frank pulmonary edema (three patients). The edema generally resolved within 4 days after the termination of therapy (four patients), however, one patient developed edema and arrhythmias approximately 7 days after interleukin-2 therapy ended. Seven of the eight patients had either cardiac arrythmias or angina. The mechanisms that contribute to the pathogenesis of these cardiac complications with interleukin-2 therapy remain unclear. The development of pulmonary edema is thought to be caused by capillary leakage and cardiac pulmonary edema due to cardiac toxicity of the drug. The radiologic appearances of these types of pulmonary edema were indistinguishable from one another and from other causes of pulmonary edema. Our study shows that interleukin-2 can cause pulmonary edema, cardiac arrhythmias, and unstable angina. The severity of these conditions is unrelated to dose.


MRI appearances of pure epithelial papillary serous borderline ovarian tumours.
Borderline epithelial ovarian tumours (BOT) represent 15-20% of all non-benign ovarian epithelial neoplasms. Compared to malignant ovarian tumours, they usually present at a younger age and carry a far superior prognosis. Fertility-conserving surgery is an important treatment option for patients with BOT. Ultrasound and CT are both widely available and play roles in the initial investigation and staging of BOT, respectively. However, lack of soft-tissue contrast limits their ability to characterize BOT. MRI can facilitate recognition of pure epithelial serous BOT (SBOT), including the cystic papillary and surface papillary subtypes. An abundance of hyperintense papillary projections with low signal internal branching and ovarian stroma preservation with a hypointense ovarian capsular margin on T2-weighted imaging are features strongly suggestive of SBOT. In this review we will discuss the general morphological features of SBOT, the benefits and drawbacks of ultrasound and CT in the initial work-up, and the principal MRI features enabling recognition of surface papillary and cystic papillary SBOT.


[IPSS-QOL questionnaire in assessing symptoms and quality of life in patients with anterior urethral stricture].
The IPSS-QOL questionnaire is frequently used to assess symptoms and quality of life of men with urethral strictures. However, the psychometric properties of the questionnaire in assessing these patients have not been evaluated. To test the psychometric properties of the IPSS-QoL questionnaire in assessing patients with anterior urethral strictures. Thirty five men with anterior urethral strictures self-completed the IPSS-QoL questionnaire. The reliability of the questionnaire was estimated by computing Cronbachs coefficient and the "point-scale" correlation coefficients. Validity was assessed by the "external criteria" - the correlations between the questionnaire scores and objective indicators - maximum urinary flow rate (Qmax) and residual urine volume (Ures), between QoL scores and index values and EQ-5D scores using a VAS rating scale. The content validity of the IPSS-QoL was assessed by experts and patients: the storage symptoms were found insignificant for patients with anterior urethral stricture, while the symptoms of primary importance (post-micturition dribbling) were not covered. Cronbachs coefficient of reliability was 0.65 (0.55-0.69 with one of the questions removed), i.e. it was below the generally accepted threshold of 0.7. The "point-scale" correlation coefficients ranged from 0.146 to 0.585; for 2 of the 7 questions they were lower, than the conventional threshold of 0.2, showing the internal inconsistencies of the questionnaire. The construct validity assessment showed no correlation between the questionnaire scores and objective indicators Qmax (R=0.178, p=0.306), Ures (R=-0.074, p=0.673). Correlations between QoL scores and index values and EQ-5D scores on the VAS were weak and statistically insignificant: R=-0.26, p=0.18 and R=-0.21, p=0.27, respectively. IPSS-QoL questionnaire in assessing men with anterior urethral stricture does not have sufficient reliability and validity. Its design does not allow for adequate assessment of all the symptoms, reliability indices are unsatisfactory, the questionnaire scores do not correlate with objective indicators. This questionnaire cannot be recommended for evaluating health status and quality of life of this category of patients.