[Prevalence of self-reported vaginal discharge and associated factors in pregnant women].
This study aims to determine the prevalence self-reported abnormal vaginal discharge and to identify associated risk factors in pregnant women in the municipality of Rio Grande, Rio Grande do Sul State, Brazil. A standardized questionnaire was applied to all pregnant women admitted for delivery in local maternity hospitals. The chi-square test was used to compare proportions, and Poisson regression was applied using multivariate analysis. Prevalence of vaginal discharge was 40%. Adjusted analysis showed the following prevalence ratios for vaginal discharge: 1.6 (1.4-1.8) for adolescents; 1.3 (1.1-1.6) for 8 years of schooling or less; 1.3 (1.1-1.5) for alcohol consumption; 2.0 (1.8-2.2) for vaginal discharge in the previous pregnancy; 1.4 (1.3-1.6) for urinary tract infection in the current pregnancy; and 0.8 (0.7-0.9) for history of prematurity. Local health services should target adolescent women, those with low schooling or low family income, and those with a history of vaginal discharge in the previous pregnancy or urinary tract infection in the current pregnancy.


Open Abdomen in Trauma and Critical Care.
The open abdomen technique and temporary abdominal closure after damage control surgery is fast becoming the standard of care for managing intra-abdominal bleeding and infectious or ischemic processes in critically ill patients. Expansion of this technique has evolved from damage control surgery in severely injured trauma patients to use in patients with abdominal compartment syndrome due to acute pancreatitis and other disorders. Subsequent therapies after use of the open abdomen technique and temporary abdominal closure are resuscitation in the intensive care unit and planned reoperation to manage the underlying cause of bleeding, infection, or ischemia. Determining the need for this potentially lifesaving intervention and managing the wound after the open abdomen has been created are all within the realm of critical care nurses. Case studies illustrate the implementation of the open abdomen technique and patient management strategies.


The role of intracellular zinc release in aging, oxidative stress, and Alzheimer's disease.
Brain aging is marked by structural, chemical, and genetic changes leading to cognitive decline and impaired neural functioning. Further, aging itself is also a risk factor for a number of neurodegenerative disorders, most notably Alzheimer's disease (AD). Many of the pathological changes associated with aging and aging-related disorders have been attributed in part to increased and unregulated production of reactive oxygen species (ROS) in the brain. ROS are produced as a physiological byproduct of various cellular processes, and are normally detoxified by enzymes and antioxidants to help maintain neuronal homeostasis. However, cellular injury can cause excessive ROS production, triggering a state of oxidative stress that can lead to neuronal cell death. ROS and intracellular zinc are intimately related, as ROS production can lead to oxidation of proteins that normally bind the metal, thereby causing the liberation of zinc in cytoplasmic compartments. Similarly, not only can zinc impair mitochondrial function, leading to excess ROS production, but it can also activate a variety of extra-mitochondrial ROS-generating signaling cascades. As such, numerous accounts of oxidative neuronal injury by ROS-producing sources appear to also require zinc. We suggest that zinc deregulation is a common, perhaps ubiquitous component of injurious oxidative processes in neurons. This review summarizes current findings on zinc dyshomeostasis-driven signaling cascades in oxidative stress and age-related neurodegeneration, with a focus on AD, in order to highlight the critical role of the intracellular liberation of the metal during oxidative neuronal injury.


Recurrent structural RNA motifs, Isostericity Matrices and sequence alignments.
The occurrences of two recurrent motifs in ribosomal RNA sequences, the Kink-turn and the C-loop, are examined in crystal structures and systematically compared with sequence alignments of rRNAs from the three kingdoms of life in order to identify the range of the structural and sequence variations. Isostericity Matrices are used to analyze structurally the sequence variations of the characteristic non-Watson-Crick base pairs for each motif. We show that Isostericity Matrices for non-Watson-Crick base pairs provide important tools for deriving the sequence signatures of recurrent motifs, for scoring and refining sequence alignments, and for determining whether motifs are conserved throughout evolution. The systematic use of Isostericity Matrices identifies the positions of the insertion or deletion of one or more nucleotides relative to the structurally characterized examples of motifs and, most importantly, specifies whether these changes result in new motifs. Thus, comparative analysis coupled with Isostericity Matrices allows one to produce and refine structural sequence alignments. The analysis, based on both sequence and structure, permits therefore the evaluation of the conservation of motifs across phylogeny and the derivation of rules of equivalence between structural motifs. The conservations observed in Isostericity Matrices form a predictive basis for identifying motifs in sequences.


MutS protein-based fiber optic particle plasmon resonance biosensor for detecting single nucleotide polymorphisms.
A new biosensing method is presented to detect gene mutation by integrating the MutS protein from bacteria with a fiber optic particle plasmon resonance (FOPPR) sensing system. In this method, the MutS protein is conjugated with gold nanoparticles (AuNPs) deposited on an optical fiber core surface. The target double-stranded DNA containing an A and C mismatched base pair in a sample can be captured by the MutS protein, causing increased absorption of green light launching into the fiber and hence a decrease in transmitted light intensity through the fiber. As the signal change is enhanced through consecutive total internal reflections along the fiber, the limit of detection for an AC mismatch heteroduplex DNA can be as low as 0.49 nM. Because a microfluidic chip is used to contain the optical fiber, the narrow channel width allows an analysis time as short as 15 min. Furthermore, the label-free and real-time nature of the FOPPR sensing system enables determination of binding affinity and kinetics between MutS and single-base mismatched DNA. The method has been validated using a heterozygous PCR sample from a patient to determine the allelic fraction. The obtained allelic fraction of 0.474 reasonably agrees with the expected allelic fraction of 0.5. Therefore, the MutS-functionalized FOPPR sensor may potentially provide a convenient quantitative tool to detect single nucleotide polymorphisms in biological samples with a short analysis time at the point-of-care sites.


Intergenerational exploration of traditional practices affecting child health: A phenomenological study.
All over the world, various traditional practices affect child health. The aim of our research was to explore the changes in traditional practices that affect child health between generations and to investigate the life experiences of generations in depth. Using a phenomenological design, this study was conducted with semi-structured interviews with families of both generations (mothers and daughters). The study was written based on the COREQ checklist. Four themes (traditional practices and intergenerational differences, beliefs/emotions related to traditional practices, influence factors in traditional practices, traditional methods in child care) and fourteen sub-themes (change in practices between generations, intergenerational transmission of traditional practices, beliefs in perceived benefits, skepticism and disbelief attitude, emotional reactions and perceiving as unnecessary, mother/mother in-law, traditional knowledge from mothers and grandmothers, family elders, the role of the internet and social media, spiritual practices, use of herbal products, alternative applications to medicines, relaxing applications, health consequences of traditional practices) were generated from the data. According to the findings, some harmless traditional practices are still relevant across generations, while harmful practices are mostly abandoned by new generations. The level of education and access to information has led the new generation to question traditional practices and show more interest in scientific knowledge-based methods. This research can contribute to advances in child health by helping us understand beliefs, feelings, and influencing factors related to traditional practices. Maternal education and community awareness-raising campaigns can be used to reduce harmful traditional practices.


Molecular cytogenetic analysis of archival uveal melanoma with known clinical outcome.
Uveal melanoma (UM) is the most common primary intraocular tumor in the Western world. Cytogenetically, this tumor is characterized by typical chromosomal aberrations such as loss of 1p, 3, and 6q, and gain of 6p and 8q. Routinely, karyotyping and fluorescent in situ hybridization (FISH) on fresh tumor-biopsies are used to identify chromosomal changes. In addition, archival UM samples can be examined using comparative genomic hybridization (CGH). In the presented study, we used CGH on a series of 46 archival uveal melanomas to identify chromosomal changes. In 44 tumors aberrations were present and classic prognostic markers as loss of 1p (12 tumors, 26.1%), monosomy 3 (26 tumors, 56.5%), loss of 6q (10 tumors, 21.7%), and gain of chromosome arm 8q (27 tumors, 58.7%) were observed. Gain of chromosome arms 18q or 21q was found in three UMs. Multiplex ligation-dependent probe amplification (MLPA), a novel technique in UM, was performed to verify this low number of chromosome 18 and 21 abnormalities, but we could not confirm the previously reported gain of 18q11.2 and 21q11.2 as poor prognostic factors in UM.


Forensic STR profile of two endogamous populations of Madhya Pradesh, India.
Genotypic polymorphism studies at 15 highly polymorphic short tandem repeat (STR) loci were carried out in two populations belonging to one caste and one tribal group of Madhya Pradesh, in central region of India. These include 110 individuals from Brahmin caste (Kanyakubj) and 89 from Gond tribe (Ojha). The 15 loci studied are: 13 CODIS STR core markers, i.e., D8S1179, D3S1358, D21S11, D7S820, CSF1PO, vWA, TPOX, D18S51, THO1, D13S317, D16S539, D5S818, FGA and 2 other loci D19S433 and D2S1338. The results show departure from the Hardy-Weinberg equilibrium with respect to two loci, viz., D3S1358 and FGA in Gond tribe and at seven loci, viz., D21S11, D19S433, TPOX, D18S51, THO1, D5S818, and FGA in Brahmin caste. Population differentiation tests between the two studied populations and with seven neighboring populations (4 tribes and 3 castes - two middle castes and one Deshasth Brahmin) revealed significant differences at several loci. The power of discrimination of the microsatellite markers used was found to be high for both the populations. The data thereof is of immense significance for forensic result interpretation and is an addition to the existing autosomal STR database on Indian population.


Population differentiation in Daphnia alters community assembly in experimental ponds.
Most studies of community assembly ignore how genetic differentiation within species affects their colonization and extinction. However, genetic differentiation in ecologically relevant traits may be substantial enough to alter the colonization and extinction processes that drive community assembly. We measured significant molecular genetic and quantitative trait differentiation among three Daphnia pulex × pulicaria populations in southwestern Michigan ponds and investigated whether this differentiation could alter the assembly of pond zooplankton communities in experimental mesocosms. In this study, we monitored the invasion success of different D. pulex × pulicaria populations after their introduction into an established zooplankton community. We also monitored the invasion success of a diverse array of zooplankton species into different D. pulex × pulicaria populations. Zooplankton community composition depended on the D. pulex × pulicaria source population. Daphnia pulex × pulicaria from one population failed to invade zooplankton communities, while those from other populations successfully invaded similar communities. If population differentiation in other species plays a role in community assembly similar to that demonstrated in our study, assembly may be more sensitive to evolutionary processes than has been previously generally considered.


Diagnostic Accuracy of Right Bronchial Infiltration on Chest X-rays in Diagnosing COVID-19 Patients in the Early Stage of the Disease.
Purpose SARS-CoV-2 has been a diagnostic challenge for healthcare setups worldwide since 2019 due to its proximity to a myriad of pathological processes. Although reverse transcription - polymerase chain reaction (RT-PCR) and high-resolution computed tomography (HRCT) have helped in the diagnosis of the disease, they are not as widely available as chest X-rays. This study aims to investigate the diagnostic accuracy of right bronchial infiltration in chest X-ray in diagnosing COVID-19. Material and methods This was a validation study conducted in a single center in Riyadh, Saudi Arabia. A total of 114 patients were enrolled according to the selection criteria of the study. Consent was waived off on the condition of confidentiality maintenance as per the ethical review board. X-rays of suspected patients were viewed and analyzed by two blinded consultant radiologists. Patients were followed for their RT-PCR reports. Data were entered and analyzed in SPSS Statistics v.23.0 (IBM Corp., Armonk, USA). Results Among the 114 patients, the mean age was 46.2±17.3 years and 85 (74.6%) were males. The total number of COVID-19-positive patients were 82 (71.9%) while the patients presenting with right bronchial infiltration (RBI) were 94 (82.5%). RBI was significantly associated with the presence and absence of COVID-19 on PCR (p<0.001) and the presence of comorbidities (p<0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the sign were 84.04%, 85.00%, 96.34%, 53.12%, and 84.21%, respectively. Conclusions RBI can be used as a diagnostic sign in X-rays for early identification of COVID-19 positive patients. This feature can be used in the triage of patients. This would decrease the spread of disease by providing early time to intervene to isolate patients.


Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management.
Duchenne muscular dystrophy (DMD) is a severe, progressive disease that affects 1 in 3600-6000 live male births. Although guidelines are available for various aspects of DMD, comprehensive clinical care recommendations do not exist. The US Centers for Disease Control and Prevention selected 84 clinicians to develop care recommendations using the RAND Corporation-University of California Los Angeles Appropriateness Method. The DMD Care Considerations Working Group evaluated assessments and interventions used in the management of diagnostics, gastroenterology and nutrition, rehabilitation, and neuromuscular, psychosocial, cardiovascular, respiratory, orthopaedic, and surgical aspects of DMD. These recommendations, presented in two parts, are intended for the wide range of practitioners who care for individuals with DMD. They provide a framework for recognising the multisystem primary manifestations and secondary complications of DMD and for providing coordinated multidisciplinary care. In part 1 of this Review, we describe the methods used to generate the recommendations, and the overall perspective on care, pharmacological treatment, and psychosocial management.


Independent component analysis applied to feature extraction from colour and stereo images.
Previous work has shown that independent component analysis (ICA) applied to feature extraction from natural image data yields features resembling Gabor functions and simple-cell receptive fields. This article considers the effects of including chromatic and stereo information. The inclusion of colour leads to features divided into separate red/green, blue/yellow, and bright/dark channels. Stereo image data, on the other hand, leads to binocular receptive fields which are tuned to various disparities. The similarities between these results and the observed properties of simple cells in the primary visual cortex are further evidence for the hypothesis that visual cortical neurons perform some type of redundancy reduction, which was one of the original motivations for ICA in the first place. In addition, ICA provides a principled method for feature extraction from colour and stereo images; such features could be used in image processing operations such as denoising and compression, as well as in pattern recognition.


In vitro and in vivo antiproliferative effect of a combination of ultraviolet-A and alkoxy furocoumarins isolated from Umbelliferae medicinal plants, in melanoma cells.
We examined the effects of six furocoumarins with alkoxy groups at the C-5 or C-8 position isolated from Umbelliferae medicinal plants on cell proliferation, and their mechanisms of action against B16F10 melanoma cells or in melanin-possessing hairless mice implanted with B16F10 cells, under UVA irradiation. Three furocoumarins with an alkoxy group at C-5, isoimperatorin (1), oxypeucedanin (2) and oxypeucedanin hydrate (3), showed antiproliferative activity and caused G2/M arrest at concentrations of 0.1-10.0 μm. Furthermore, three furocoumarins with an alkoxy group at C-8, imperatorin (4), heraclenin (5) and heraclenol (6), inhibited the proliferation of melanoma cells and cell cycle at G2/M at concentrations of 0.1-1.0 μm. UVA plus 1, 2, 3, 4 and 6 reduced tumor growth and final tumor weight in B16F10-bearing mice at a dose of 0.3, 0.5 or 1.0 mg kg(-1) (intraperitoneal injection). UVA plus 1, 3 and 6 increased Chk1 phosphorylation and reduced cdc2 (Thr 161) phosphorylation in melanoma cells. We suggest that the antitumor actions of UVA plus furocoumarins with an alkoxy group at C-5 or C-8 were due to G2/M arrest of the cell cycle by an increase in phosphor-Chk1 and decrease in phospho-cdc2.


Adoption of focused ultrasound thalamotomy for essential tremor: why so much fuss about FUS?
Focused ultrasound (FUS) was approved as a new treatment modality for essential tremor (ET) in 2016. The goal of this study was to quantify FUS adoption for ET and understand its drivers. The adoption of the various surgical options for ET was estimated using three measures: the number of presentations on the various surgical treatments for ET at specialised international meetings, the number of original papers published as identified by literature searches and the number of thalamotomy procedures performed worldwide for ET as provided by device manufacturers' registries. First, we found that the number of presentations related to lesioning procedures is increasing relative to deep brain stimulation (DBS) at international meetings. Second, there are already more publications on FUS (93) than stereotactic radiosurgery (SRS) (68) or radiofrequency (43) for ET, although they still lag behind DBS papers (750). Third, the number of annual FUS thalamotomies performed for ET (n>1200 in 2019) in 44 centres has surpassed the annual procedures across 342 Gamma Knife units (n<400, 2018) but is yet to reach the number of DBS cases for ET estimated at over 2400/year. FUS is being rapidly adopted for the treatment of ET. We hypothesise that its perceived minimally invasive nature coupled with the ability to perform intraoperative clinical assessments, its immediate effects and active marketing efforts are contributing factors. As lesioning modalities for the treatment of ET are reappraised, the superior popularity of FUS over SRS appears to arise for reasons other than differences in clinical outcomes.


Cochlear implantation in patients with neurofibromatosis type 2: variables affecting auditory performance.
To investigate cochlear implant performance outcomes among patients with Neurofibromatosis type 2 (NF2). Retrospective case series, patient questionnaire, and systematic review of the literature. Tertiary academic referral center. All patients with NF2 having an anatomically intact ipsilateral cochlear nerve who underwent cochlear implantation (CI). Cochlear implantation. Postimplantation audiometric performance and patient perceived benefit. Ten patients met study criteria. The median duration of follow-up after CI was 42 months (mean, 46.9 mo; range, 12-97 mo). Five patients received previous microsurgical resection of their ipsilateral vestibular schwannoma, 4 underwent previous stereotactic radiosurgery, and 1 patient had no tumor treatment before CI. Nine subjects achieved sound awareness, 6 attained open-set speech recognition and 7 are daily users. Variables including prolonged auditory deprivation, cochlear ossification, unfavorable electrical promontory stimulation testing, and useful contralateral hearing were associated with poor cochlear implant performance. No statistical associations were found between open-set recognition capacity and previous tumor management strategy, surgical approach, or ipsilateral tumor size. Cochlear implantation is an attractive alternative to auditory brainstem implantation for hearing rehabilitation in patients with NF2. Approximately 70% of patients achieve open-set speech discrimination, many scoring at the ceiling of audiometric testing. Given a favorable risk profile and superior audiometric outcomes, CI should be strongly considered in patients with nonserviceable hearing who have an anatomically intact cochlear nerve, whereas auditory brainstem implantation should be reserved for patients with evidence of cochlear nerve loss. Akin to conventional cochlear implant recipients, prolonged hearing loss, unfavorable electrophysiological testing, and cochlear ossification may predict poor subject performance. Finally, useful hearing in the contralateral ear may present a barrier to daily device use.


Single-cell RNA sequencing combined with single-cell proteomics identifies the metabolic adaptation of islet cell subpopulations to high-fat diet in mice.
Islets have complex heterogeneity and subpopulations. Cell surface markers representing alpha, beta and delta cell subpopulations are urgently needed for investigations to explore the compositional changes of each subpopulation in obesity progress and diabetes onset, and the adaptation mechanism of islet metabolism induced by a high-fat diet (HFD). Single-cell RNA sequencing (scRNA-seq) was applied to identify alpha, beta and delta cell subpopulation markers in an HFD-induced mouse model of glucose intolerance. Flow cytometry and immunostaining were used to sort and assess the proportion of each subpopulation. Single-cell proteomics was performed on sorted cells, and the functional status of each alpha, beta and delta cell subpopulation in glucose intolerance was deeply elucidated based on protein expression. A total of 33,999 cells were analysed by scRNA-seq and clustered into eight populations, including alpha, beta and delta cells. For alpha cells, scRNA-seq revealed that the Ace2low subpopulation had downregulated expression of genes related to alpha cell function and upregulated expression of genes associated with beta cell characteristics in comparison with the Ace2high subpopulation. The impaired function and increased fragility of ACE2low alpha cells exposure to HFD was further suggested by single-cell proteomics. As for beta cells, the CD81high subpopulation may indicate an immature signature of beta cells compared with the CD81low subpopulation, which had robust function. We also found differential expression of Slc2a2 in delta cells and a potentially stronger cellular function and metabolism in GLUT2low delta cells than GLUT2high delta cells. Moreover, an increased proportion of ACE2low alpha cells and CD81low beta cells, with a constant proportion of GLUT2low delta cells, were observed in HFD-induced glucose intolerance. We identified ACE2, CD81 and GLUT2 as surface markers to distinguish, respectively, alpha, beta and delta cell subpopulations with heterogeneous maturation and function. The changes in the proportion and functional status of islet endocrine subpopulations reflect the metabolic adaptation of islets to high-fat stress, which weakened the function of alpha cells and enhanced the function of beta and delta cells to bring about glycaemic homeostasis. Our findings provide a fundamental resource for exploring the mechanisms maintaining each islet endocrine subpopulation's fate and function in health and disease. The scRNA-seq analysis datasets from the current study are available in the Gene Expression Omnibus (GEO) repository under the accession number GSE203376.


Counteracting Roles of Lipidic Aldehydes and Phenolic Antioxidants on Soy Protein Oxidation Defined by a Chemometric Survey of Solvent and Mechanically Extracted Soybean Meals.
Soybean meal (SBM) is a premier source of protein for feeding food-producing animals. However, its nutritional value can be compromised by protein oxidation. In this study, a total of 54 sources of solvent extracted SBM (SSBM) and eight sources of mechanically extracted SBM (MSBM), collected from different commercial producers and geographic locations in the United States during the years 2020 and 2021, were examined by chemometric analysis to determine the extent of protein oxidation and its correlation with soybean oil extraction methods and non-protein components. The results showed substantial differences between SSBM and MSBM in the proximate analysis composition, protein carbonyl content, lipidic aldehydes, and antioxidants, as well as subtle differences between 2020 SSBM and 2021 SSBM samples in protein oxidation and moisture content. Correlation analysis further showed positive correlations between protein carbonyl content and multiple lipid parameters, including the ether extract, p-anisidine value, individual aldehydes, and total aldehydes. Among the antioxidants in SBM, negative correlations with protein carbonyl content were observed for total phenolic content and isoflavone glycoside concentrations, but not for Trolox equivalent antioxidant capacity (TEAC), α-tocopherol, and γ-tocopherol. Overall, soybean oil extraction methods, together with other factors such as enzyme treatment and environmental conditions, can significantly affect the proximate analysis composition, the protein and lipid oxidation status, and the antioxidant profile of SBM. Lipidic aldehydes and phenolic antioxidants play counteracting roles in the oxidation of soy protein. The range of protein carbonyl content measured in this study could serve as a reference to evaluate the protein quality of SBM from various sources used in animal feed.


Infrared Spectroscopy: A New Frontier in Hematological Disease Diagnosis.
Hematological diseases, due to their complex nature and diverse manifestations, pose significant diagnostic challenges in healthcare. The pressing need for early and accurate diagnosis has driven the exploration of novel diagnostic techniques. Infrared (IR) spectroscopy, renowned for its noninvasive, rapid, and cost-effective characteristics, has emerged as a promising adjunct in hematological diagnostics. This review delves into the transformative role of IR spectroscopy and highlights its applications in detecting and diagnosing various blood-related ailments. We discuss groundbreaking research findings and real-world applications while providing a balanced view of the potential and limitations of the technique. By integrating advanced technology with clinical needs, we offer insights into how IR spectroscopy may herald a new era of hematological disease diagnosis.


Canonical non-homologous end joining in mitosis induces genome instability and is suppressed by M-phase-specific phosphorylation of XRCC4.
DNA double-strand breaks (DSBs) can be repaired by one of two major pathways-non-homologous end-joining (NHEJ) and homologous recombination (HR)-depending on whether cells are in G1 or S/G2 phase, respectively. However, the mechanisms of DSB repair during M phase remain largely unclear. In this study, we demonstrate that transient treatment of M-phase cells with the chemotherapeutic topoisomerase inhibitor etoposide induced DSBs that were often associated with anaphase bridge formation and genome instability such as dicentric chromosomes. Although most of the DSBs were carried over into the next G1 phase, some were repaired during M phase. Both NHEJ and HR, in particular NHEJ, promoted anaphase-bridge formation, suggesting that these repair pathways can induce genome instability during M phase. On the other hand, C-terminal-binding protein interacting protein (CtIP) suppressed anaphase bridge formation, implying that CtIP function prevents genome instability during mitosis. We also observed M-phase-specific phosphorylation of XRCC4, a regulatory subunit of the ligase IV complex specialized for NHEJ. This phosphorylation required cyclin-dependent kinase (CDK) activity as well as polo-like kinase 1 (Plk1). A phosphorylation-defective XRCC4 mutant showed more efficient M-phase DSB repair accompanied with an increase in anaphase bridge formation. These results suggest that phosphorylation of XRCC4 suppresses DSB repair by modulating ligase IV function to prevent genome instability during M phase. Taken together, our results indicate that XRCC4 is required not only for the promotion of NHEJ during interphase but also for its M-phase-specific suppression of DSB repair.


Open versus arthroscopic acromioclavicular joint resection: a systematic review and meta-analysis.
The purpose of this study was to perform a meta-analysis comparing open and arthroscopic surgical techniques for distal clavicle resection. A systematic review of Medline, Embase, Scopus, and Google Scholar identified relevant publications in the English and German literature between 1997 and 2017. All included studies were levels I-IV, describing both treatments, with a minimum of 12 month follow-up, had at least one validated outcome score and documented patient recruitment, study design, demographic details, and surgical technique. Studies were excluded if they were only abstracts or conference proceedings, involved revision procedures, or the loss to follow-up exceeded 20%. Publication bias and risk of bias were assessed using the Cochrane Collaboration tools, and heterogeneity was assessed using the I2 statistic. Four studies (n = 319 patients) met the criteria for inclusion. The pooled estimate for clinical outcomes (Constant, ASES) demonstrated no significant differences (SMD 0.323, I2 = 0%, p = 0.065) between open and arthroscopic resection, although the analysis favored open resection. The pooled estimate for clinical outcomes (SST) also demonstrated no significant differences (SMD 0.744, I2 = 49.82%, p = 0.144) between open and arthroscopic resection, but the analysis again favored open resection. The pooled estimate for VAS assessment of pain demonstrated no differences (SMD 0.217, I2 = 58.96%; p = 0.404) between open and arthroscopic resection. The results of this study suggest that similar functional and clinical outcomes can be achieved with either open or arthroscopic distal clavicle resection. The observed trend that open resection may have a more favorable outcome warrants further investigation. Level 3; systematic review and meta-analysis.


Cloacal dysgenesis: related anomalies and pregnancies.
Cloacal dysgenesis is an extremely rare birth deformity that occurs only in female infants. It results when the normal interposition of the müllerian system between the urinary and alimentary tracts fails to occur between the sixth and eighth weeks of fetal development. A case is presented of an infant who was born with a cloaca and survived temporizing surgical procedures that produced a neorectovagina as a corrective measure. Incredibly, at age 28, conception occurred. A cesarean section was an absolute requirement but would directly expose the peritoneal cavity to gross contamination by bowel content. Nonetheless, a supravesical extraperitoneal cesarean section was successfully completed. After 6 months concept again occurred. The same surgical procedures were repeated at term. In each instance, the newborn was normal and survived.


Overexpression of Prokineticin 2 in Transgenic Mice Leads to Reduced Circadian Behavioral Rhythmicity and Altered Molecular Rhythms in the Suprachiasmatic Clock.
In mammals, the master pacemaker driving circadian rhythms is thought to reside in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. A clear view of molecular clock mechanisms within the SCN neurons has been elucidated. In contrast, much less is known about the output mechanism by which the SCN circadian pacemaker sends timing information for eventual control of physiological and behavioral rhythms. Two secreted molecules, prokineticin 2 (PK2) and vasopressin, that are encoded by respective clock-controlled genes, have been indicated as candidate SCN output molecules. Several lines of evidence have emerged that support the role of PK2 as an output signal for the SCN circadian clock, including the reduced circadian rhythms in mice that are deficient in PK2 or its receptor, PKR2. In the current study, transgenic mice with the overexpression of PK2 have been generated. These transgenic mice displayed reduced oscillation of the PK2 expression in the SCN and decreased amplitude of circadian locomotor rhythm, supporting the important signaling role of PK2 in the regulation of circadian rhythms. Altered molecular rhythms were also observed in the SCN in the transgenic mice, indicating that PK2 signaling also regulates the operation of core clockwork. This conclusion is consistent with recent reports showing the likely signaling role of PK2 from the intrinsically photosensitive retinal ganglion cells to SCN neurons. Thus, PK2 signaling plays roles in both the input and the output pathways of the SCN circadian clock.


[The functional maturation of Langerhans cells in CTL induction during tissue culture].
In the previous report, we investigated the effects of tissue culture on the APC function of murine epidermal Langerhans cells (LC) in the induction of allo-CTL in vitro, and found that (1) cultured ear LC expressed increased amounts of Ia antigens on their cell surface, and (2) they induced extremely enhanced levels of CTL over those produced by freshly prepared ear LC and also (3) cultured tail LC were proved to be able to induce CTL for the first time. It seemed that tissue culture decreased the functional heterogeneity among the murine ear LC and tail LC in addition to that among Ia+ APC in spleen and in epidermis. In this study, we investigated the culture conditions that increase the APC function of LC. Our data indicate that LC cultured with dermal components exhibited more enhanced APC function than LC cultured in single cell suspension with only epidermal cells. Recent studies indicate that IL-1 and GM-CSF, which keratinocytes release, are essential for freshly prepared LC to mature into highly efficient APC that resemble splenic dendritic cells. We found dermal factors are more important than epidermal ones for LC to mature in tissue culture.


Use of operon fusions to examine the regulation of the L-1,2-propanediol oxidoreductase gene of the fucose system in Escherichia coli K12.
Escherichia coli K12 growing anaerobically on L-fucose excretes L-1,2-propanediol as a fermentation product whose formation is catalysed by an inducible NAD-linked oxidoreductase. The activity of this enzyme is highly induced only during anaerobic growth. Three bacterial strains bearing a hybrid operon with the structural genes for lactose utilization (lacZYA) fused to the promoter of the propanediol oxidoreductase gene (fucO) were constructed to test whether or not transcriptional control was involved. In contrast to propanediol oxidoreductase of wild-type cells, beta-galactosidase in the phi(fuc-lac) strains was induced by fucose to high levels both aerobically and anaerobically. Data from this work are in accord with the previous report that the enzyme protein (assayed by specific antibodies) was induced both aerobically and anaerobically, but that only in anaerobically grown cells was the oxidoreductase catalytically active. In the present study, we found that the oxidoreductase induced anaerobically in wild-type cells remained enzymically active during aerobic growth in the absence of fucose. On the other hand, wild-type cells grown aerobically in the presence of fucose and then allowed limited anaerobic growth on glucose did not gain any oxidoreductase activity. The mechanism of this post-transcriptional control remains to be discovered.


Simplified technique for auxiliary orthotopic liver transplantation using a whole graft.
Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. To describe an alternative technique to auxiliary liver transplant on acute liver failure. Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O'Grady's criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. The procedure improved liver function and decreased intracranial hypertension in the postoperative period. This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil.


Survival of probiotic adjunct cultures in cheese and challenges in their enumeration using selective media.
Various selective media for enumerating probiotic and cheese cultures were screened, with 6 media then used to study survival of probiotic bacteria in full-fat and low-fat Cheddar cheese. Commercial strains of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus paracasei, or Bifidobacterium lactis were added as probiotic adjuncts. The selective media, designed to promote growth of certain lactic acid bacteria (LAB) over others or to differentiate between LAB, were used to detect individual LAB types during cheese storage. Commercial strains of Lactococcus, Lactobacillus, and Bifidobacterium spp. were initially screened on the 6 selective media along with nonstarter LAB (NSLAB) isolates. The microbial flora of the cheeses was analyzed during 9 mo of storage at 6°C. Many NSLAB were able to grow on media presumed selective for Lactococcus, Bifidobacterium spp., or Lb. acidophilus, which became apparent after 90 d of cheese storage, Between 90 and 120 d of storage, bacterial counts changed on media selective for Bifidobacterium spp., suggesting growth of NSLAB. Appearance of NSLAB on Lb. casei selective media [de man, Rogosa, and Sharpe (MRS)+vancomycin] occurred sooner (30 d) in low-fat cheese than in full-fat control cheeses. Differentiation between NSLAB and Lactococcus was achieved by counting after 18 to 24h when the NSLAB colonies were only pinpoint in size. Growth of NSLAB on the various selective media during aging means that probiotic adjunct cultures added during cheesemaking can only be enumerated with confidence on selective media for up to 3 or 4 mo. After this time, growth of NSLAB obfuscates enumeration of probiotic adjuncts. When adjunct Lb. casei or Lb. paracasei cultures are added during cheesemaking, they appear to remain at high numbers for a long time (9 mo) when counted on MRS+vancomycin medium, but a reasonable probability exists that they have been overtaken by NSLAB, which also grow readily on this medium. Enumeration using multiple selective media can provide insight into whether it is the actual adjunct culture or a NSLAB strain that is being enumerated.


Hypnotic susceptibility, mood state, and cardiovascular reactivity.
In this study we explored the relationship between hypnotic susceptibility measured with the Harvard Group Scale of Hypnotic Susceptibility (HGSHS) and cardiovascular parameters. After assessing their degree of hypnotic susceptibility, we induced 21 female students into happy mood states and into sad mood states. During the mood state induction we monitored blood pressure, heart rate, and cardiac vagal tone continuously. The study demonstrated a strong relationship between hypnotic susceptibility and both cardiac vagal tone and heart rate reactivity. Subjects with lower heart rate and greater vagal tone during baseline and greater heart rate increases during mood induction were more susceptible to hypnosis. Multiple regression analyses indicated that approximately 40% of the individual difference variance of hypnotic susceptibility was accounted for by baseline cardiac vagal tone and heart rate reactivity during mood state. The data demonstrate that autonomic tone, assessed by cardiac vagal tone and heart rate reactivity, are related to hypnotic susceptibility as measured by the HGSHS.


β1-Adrenergic receptors activate two distinct signaling pathways in striatal neurons.
Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine (NE) and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP response element binding protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. NE-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which NE and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how NE and β1-adrenergic receptors may affect striatal physiology.


Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 immune responses.
Nucleoside modified mRNA combined with Acuitas Therapeutics' lipid nanoparticles (LNPs) has been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs' ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper (Tfh) cells and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, these mice remained protected from lethal influenza and SARS-CoV-2 challenges. We further found that IL-6, unlike neutrophils, was required to generate normal Tfh cells and antibody responses, but not for protection from influenza challenge. In summary, here we bring evidence that the mRNA-LNP platform can support the induction of protective immune responses in the absence of certain innate immune cells and cytokines.


Advances in Development of Selective Antitumor Inhibitors That Target PARP-1.
Cancer is a major threat to the lives and health of people around the world, and the development of effective antitumor drugs that exhibit fewer toxic effects is an important aspect of cancer treatment. PARP inhibitors are antitumor drugs that target pathways involved in DNA-damage repair. The currently approved PARP inhibitors include olaparib, niraparib, rucaparib, talazoparib, fuzuloparib, and pamiparib. Hematological toxicities associated with the simultaneous inhibition of PARP-1 and PARP-2 have limited the clinical applications of these drugs. The present review introduces the necessity for research on the development of selective PARP-1 inhibitors from the perspective of structural and functional mechanisms of PARP-1 inhibition. A review of recently reported selective PARP-1 inhibitors provides the foundation for exploring novel strategies for designing selective PARP-1 inhibitors from the perspective of structure-activity relationships combined with computer simulations.


4D Printing of Smart Polymer Nanocomposites: Integrating Graphene and Acrylate Based Shape Memory Polymers.
The ever-increasing demand for materials to have superior properties and satisfy functions in the field of soft robotics and beyond has resulted in the advent of the new field of four-dimensional (4D) printing. The ability of these materials to respond to various stimuli inspires novel applications and opens several research possibilities. In this work, we report on the 4D printing of one such Shape Memory Polymer (SMP) tBA-co-DEGDA (tert-Butyl Acrylate with diethylene glycol diacrylate). The novelty lies in establishing the relationship between the various characteristic properties (tensile stress, surface roughness, recovery time, strain fixity, and glass transition temperature) concerning the fact that the print parameters of the laser pulse frequency and print speed are governed in the micro-stereolithography (Micro SLA) method. It is found that the sample printed with a speed of 90 mm/s and 110 pulses/s possessed the best batch of properties, with shape fixity percentages of about 86.3% and recovery times as low as 6.95 s. The samples built using the optimal parameters are further subjected to the addition of graphene nanoparticles, which further enhances all the mechanical and surface properties. It has been observed that the addition of 0.3 wt.% of graphene nanoparticles provides the best results.


Ecosystem multifunctionality increases with beta diversity in restored prairies.
The loss of biodiversity at local and larger scales has potentially dramatic effects on ecosystem functioning. Many studies have shown that ecosystem functioning depends on biodiversity, but the role of beta diversity, spatial variation in community composition, is less clear than that of local-scale (alpha) diversity. To test the hypothesis that beta diversity would increase ecosystem multifunctionality through variation in species functional traits, we gathered data on plant community composition, plant functional traits, and seven ecosystem functions across 29 restored prairies. We found that averaged multifunctionality (mean of seven ecosystem functions) increased with both taxonomic beta diversity and functional beta diversity. The abundance of the dominant species, big bluestem, played a more minor role, suggesting a limited role for the selection effect. Neither taxonomic nor functional alpha richness was associated with multifunctionality, though this finding may be sensitive to the identity of the functions included because alpha diversity was associated with some individual functions in opposing directions. These findings suggest that in systems structured largely by natural processes, beta diversity (a patchwork of functionally different plant communities) and dominant species abundance may be more important than alpha diversity in fostering ecosystem multifunctionality. These findings suggest the need for an increased focus on community heterogeneity to reestablish functional ecosystems during restoration.


Quality of life among Korean gastrointestinal cancer survivors.
The number of gastrointestinal (GI) cancer survivors has been steadily increasing owing to early diagnosis and improved cancer treatment outcomes. The quality of life (QoL) of cancer survivors can provide distinct prognostic information and represent their functioning. This study aimed to investigate the levels of symptoms, psychological distress, and QoL of GI cancer survivors, and identify factors associated with QoL. A cross-sectional survey was conducted among 145 survivors of gastric or colorectal cancer in a university-affiliated hospital, Seoul, South Korea. The questionnaire consisted of the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module, Distress Thermometer, and brief version of the World Health Organization Quality of Life Assessment Instrument. Quantile regression was used to assess the associated factors of QoL. The 10th, 25th, 50th, 75th, and 90th conditional quantiles were considered. The most common symptoms were fatigue (24.9%), numbness or tingling (17.2%), feeling bloated (17.2%), dry mouth (15.9%), and difficulty remembering (11.8%). Thirty-two percent (47/145) of the participants reported severe distress. A level of symptoms was significantly associated in the 10th and 25th quantiles, representing poor QoL. Economic burden was a significant influencing factor in all quantiles. Our results indicate that high burden from symptoms might be associated with lower QoL in GI cancer survivors, and higher economic burden from cancer treatment was associated with lower QoL. These results suggest that symptom management and support for economic difficulties should be included in the strategies to enhance the QoL of GI cancer survivors.


[Effects of antihypertensive drugs with different mechanism of action on cardiac hemodynamics in patients with artificial pacemaker].
Cardiohemodynamic effects of obsidan, nifedipin, captopril and prasosine were compared when the drugs were given in a 4-week course regarding circulation type and stimulation regime to 74 patients with artificial pacemaker suffering from mild or moderate essential hypertension. A peculiar action of obsidan, nifedipin and prasosine in cardiac pacing found at echocardiography is explained by the absence of frequency-dependent (chronotropic) cardiohemodynamic effects. Obsidan lowered blood pressure most effectively in hyperkinetic circulation. Nifedipine, captopril and prasosine were more potent in eu- and hypokinetic circulation. Reduction of arterial pressure by the above peripheral vasodilators in patients with hyperkinetic circulation results from a fall of total peripheral vascular resistance initially elevated by 16.5%, on the average. In isolated ventricular stimulation (regime VVI) vs atrial one (AAI regime) hypotensive action of the above drugs was more potent, but side effects were more frequent.


Reducing anxiety sensitivity with exercise.
Exercise interventions repeatedly have been shown to be efficacious for the treatment of depression, and initial studies indicate similar efficacy for the treatment of anxiety conditions. To further study the potential beneficial role of prescriptive exercise for anxiety-related conditions, we examined the role of exercise in reducing fears of anxiety-related sensations (anxiety sensitivity). We randomly assigned 60 participants with elevated levels of anxiety sensitivity to a 2-week exercise intervention, a 2-week exercise plus cognitive restructuring intervention, or a waitlist control condition. Assessment of outcome was completed at pretreatment, midtreatment, 1-week posttreatment, and 3-week follow-up. We found that both exercise conditions led to clinically significant changes in anxiety sensitivity that were superior to the waitlist condition, representing a large controlled effect size (d=2.15). Adding a cognitive component did not facilitate the effects of the exercise intervention. Consistent with hypotheses, changes in anxiety sensitivity mediated the beneficial effects of exercise on anxious and depressed mood. We discuss these findings in terms of the potential role of exercise as an additional psychosocial intervention for conditions such as panic disorder, where anxiety sensitivity is a prominent component of pathology.


Breast cancer and gastrointestinal metastasis. A case report and review of the literature.
Invasive lobular cancer (ILC) is the second most common type of a heterogeneous group of different histological types of invasive breast carcinoma. Breast cancer can metastatize anywhere, the most common sites are bones, liver, lungs and brain. Gastrointestinal tract (GI) metastases observed in autopsy studies account for about 6% to 18% of the overall metastases from breast cancer. We describe a 54-year old woman with recurrent ILC in the contralateral breast. She underwent right mastectomy 16 years before. After symptomatic presentation a duodenal invasion was found and subjected to diagnostic scrutiny (FDG PET/CT, diagnostic CT, MR, EGDS). In particular, we analyse if FDG PET/CT is enough accurate in the restaging of the patient. A review of our database and of the literature of similar cases were made. In this patient CT and RM were suspicious for a slow developing process of the duodenum but FDG PET/CT did not show pathological uptake in the affected duodenal tract. A highly intense focus was described in a cervical lymph node, that there isn't metastatic lesion, whereas the recurrent breast lesion had only slight increased glycolytic activity. Metastatic lobular carcinoma of the breast is a rare entity with a heterogeneous range of clinical presentations. Detection of eventual gastrointestinal metastases are complicated to assess. ILC has various scale of glycolytic activity both in the primary lesion as well in the metastatic foci. When the level of suspicion is high and there is no uptake of FDG, further investigations are necessary. Abdominal metastasis, FGD PET-TC, Lobular Breast Cancer.


EVI1 carboxy-terminal phosphorylation is ATM-mediated and sustains transcriptional modulation and self-renewal via enhanced CtBP1 association.
The transcriptional regulator EVI1 has an essential role in early hematopoiesis and development. However, aberrantly high expression of EVI1 has potent oncogenic properties and confers poor prognosis and chemo-resistance in leukemia and solid tumors. To investigate to what extent EVI1 function might be regulated by post-translational modifications we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif. In the presence of genotoxic stress EVI1-WT (SQS), but not site mutated EVI1-AQA was able to maintain transcriptional patterns and transformation potency, while under standard conditions carboxy-terminal mutation had no effect. Maintenance of hematopoietic progenitor cell clonogenic potential was profoundly impaired with EVI1-AQA compared with EVI1-WT, in particular in the presence of genotoxic stress. Exploring mechanistic events underlying these observations, we showed that after genotoxic stress EVI1-WT, but not EVI1-AQA increased its level of association with its functionally essential interaction partner CtBP1, implying a role for ATM in regulating EVI1 protein interactions via phosphorylation. This aspect of EVI1 regulation is therapeutically relevant, as chemotherapy-induced genotoxicity might detrimentally sustain EVI1 function via stress response mediated phosphorylation, and ATM-inhibition might be of specific targeted benefit in EVI1-overexpressing malignancies.


Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients.
There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P = .001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553-26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330-28.22), and remission after 12 months (OR, 5.333; 95% CI, 1.132-25.12). In an analysis of rectal tissues from treatment-naive pediatric patients with IBD, we observed activation of a type 2 immune response during the early course of UC. We were able to distinguish patients with UC from those with colon-only CD based on increased mucosal expression of genes that mediate type 2 and type 17 immune responses. Increased expression at diagnosis of genes that mediate a type 2 immune response is associated with response to therapy and remission in pediatric patients with UC.


Factors associated with attendance in a voluntary nutrition education program.
This paper examines factors associated with attendance in a National Cancer Institute-funded randomized trial of nutrition education to increase fruit and vegetable consumption among women served by the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). The study took place at 16 WIC sites in Maryland. The participants were 1528 women who were enrolled in WIC or who had children enrolled in WIC, were > or = 18 years of age, and planned to continue enrollment at that WIC site for at least 6 months (68% of eligible women approached agreed to participate). Women received personal invitations, letters, and telephone reminders from peer educators encouraging their attendance at three bimonthly nutrition sessions. Demographic data were collected in a baseline survey. Attendance data and telephone and address changes were also collected. The postintervention survey included a question regarding reasons for nonattendance. Focus groups were also held to ascertain reasons for attendance or nonattendance. Chi-square tests of trend and multiple logistic regression, adjusted for within-site correlation, were used in statistical analyses. Fifty-four percent of enrollees attended at least one session. Multiple logistic regression analysis showed increased odds of attending with higher age, breast-feeding, and/or knowledge of the recommendation to eat five or more servings of fruits and vegetables daily. There were decreased odds of attending for pregnant women who already had children. There were nonsignificant trends toward decreased attendance among unmarried women compared with married women and among blacks compared with nonblacks. Reasons given for nonattendance included withdrawal from WIC, moving, conflicting activities, negative feelings about nutrition education, and lack of transportation or child care. The results suggest that numerous barriers hinder participation in nutrition programs aimed at low-income women. These barriers should be considered by health care professionals when planning intervention programs. Overcoming these barriers presents a major challenge.


IRF7-dependent type I interferon production induces lethal immune-mediated disease in STAT1 knockout mice infected with lymphocytic choriomeningitis virus.
Following systemic infection with lymphocytic choriomeningitis virus (LCMV), STAT1 knockout (KO) mice but not wild-type, STAT2 KO, IRF9 KO, or IFNAR KO mice develop lethal disease perpetrated by CD4(+) T cells. IRF7 is a key transcriptional activator of type I IFN (IFN-I) during LCMV infection. Here, the role of IRF7 in the lethal host response to LCMV infection in STAT1 KO mice was examined. In contrast to STAT1 KO mice, STAT1/IRF7 double KO (DKO) mice survived LCMV infection with a reduced immune pathology in key organs, such as the liver and spleen. However, similar to STAT1 KO mice, STAT1/IRF7 DKO mice failed to control LCMV replication and spread. LCMV infection in STAT1 KO mice was associated with a significant elevation in the levels of a number of cytokines in serum, including IFN-Is, but this was largely absent in STAT1/IRF7 DKO mice, which had a modest increase in the levels of gamma interferon and CCL2 only. Since IRF7 is known to be a key transcriptional regulator of IFN-I gene expression, the possible role of IFN-I in lethal disease was examined further. STAT1/IFNAR DKO mice, in contrast to STAT1 KO mice, all survived infection with LCMV and exhibited little tissue immune pathology. Additionally, STAT1 KO mice that were deficient for either of the two IFN-I signaling molecules, STAT2 or IRF9, also survived LCMV infection. We conclude that the lethal immune-mediated disease resulting from LCMV infection in STAT1 KO mice is (i) dependent on IRF7-induced IFN-I production and (ii) driven by noncanonical IFN-I signaling via STAT2 and IRF9. Here we report on the basis for the novel, fatal immune-mediated disease of STAT1 KO mice infected with LCMV. Our findings show that, surprisingly, the pathogenesis of this disease is dependent on IRF7-mediated type I interferon production. Moreover, our study identifies noncanonical type I interferon signaling via STAT2 and IRF9 to be essential for the type I IFN-driven fatal disease in LCMV-infected STAT1 KO mice. These results further highlight the significance of noncanonical type I IFN signaling in the pathogenesis of host-mediated injury following viral infection.


Rutin Mediated Apoptotic Cell Death in Caski Cervical Cancer Cells via Notch-1 and Hes-1 Downregulation.
Natural dietary molecules such as flavonoids have been recognized for their immense potential in cancer therapeutics with several health benefits. Hes-1 and Notch-1 overexpression has been associated with the progression of cervical cancer. However, the apoptosis-inducing potential of one such potent flavanol against these two key components of the Notch signaling pathway in cervical cancer has not been elucidated to date. Therefore, in this study, we performed several in vitro assays to gain detailed insight about the apoptotic inducing effect of rutin as well as its modulatory effect on Notch-1 and Hes-1 in cervical cancer cells. The results indicated that rutin led to a dose-dependent antiproliferative effects on Caski cervical cancer cells. DAPI and Mitotracker red staining revealed that rutin induced significant apoptotic effects via caspase-3/9 activation, ROS generation, and alteration in Bax/Bcl2 mRNA expression. Cell cycle analysis resulted in the arrest of cell cycle progression in G0/G1 that was associated with a reduced expression of CDK4 and Cyclin D1. The gene expression analysis further revealed that rutin treatment decreases Notch-1 and Hes-1 mRNA expression. Altogether, these results showed that rutin showed potent anticancer effects in human cervical cancer Caski cells by triggering apoptosis, G0/G1 phase arrest, and downregulating the level of Notch-1 and Hes-1 of the Notch signaling pathway.


Is the prefrontal cortex necessary for delay task performance? Evidence from lesion and FMRI data.
Although the prefrontal cortex (PFC) is consistently found to be associated with various working memory processes, the necessity of the PFC for such processes remains unclear. To elucidate PFC contributions to storage and rehearsal/maintenance processes engaged during verbal working memory function, we assessed behavior of patients with lesions to the left or right lateral PFC, and neural activity of healthy young subjects during fMRI scanning, during performance of working memory tasks. We found that PFC lesions did not affect storage processes--which is consistent with the notion that posterior cortical networks can support simple retention of information. We also found that PFC lesions did not affect rehearsal/maintenance processes, which was in contrast to our finding that healthy subjects performing a verbal delayed recognition task showed bilateral PFC activation. These combined imaging and behavioral data suggest that working memory rehearsal/maintenance processes may depend on both hemispheres, which may have implications for recovery of function and development of rehabilitation therapies after frontal injury.


[Family violence, the use of drugs in the couple, from the mistreated woman's perspective].
The present study has the visibilizar purpose the violence that affects the women, having as main elements precipitants of the aggressor's violent attitude the ingest of alcohol and/or it drugs. The objectives of the present study are: to know the meanings that the woman attributes to the violence; to recognize the different factors related to the occurrence of the family violence and to identify like the consumption of drugs is processed in the couple. The study type is exploratory and descriptive, the qualitative methodology, the empiric cutting was used six women they constituted it who went to carry out its accusation to the police station of women from Lima. The discoveries show that the time of union oscillated between two months and eighteen years, happening the abuse in case the whole time of union. With regard to the type of suffering violence that of more magnitude was the physics; in a subtler way the psychological one, the sexual violence was not referred, the money and jealousy were referred as focuses desencadenantes of the discussions, those that are associated to the use of alcohol and it drugs in the aggressor. The established categories were: the type of violence undergone by the women, the context of the violence, the repercussion of the violence undergone by the women in its health and the reaction of violence undergone by means of the denunciation. As main conclusions we have that the violence against the women is revealed like social and sanitary topic, with repercussions in the morbi-mortality and in terms of warm of the women's life, in the field of the health, it is necessary to recognize the women in situations of violence, to consider as factors of risk for the couple the use of the alcohol and drugs, the women hide for shame the problem that you/they live, the personnel of health it should be able to diagnose the violence in their different forms, expressed by complaints or chronic pains without apparent causes.


Advanced maternal age. Part I: obstetric complications.
More women are postponing pregnancy into the fourth and fifth decades of life for a variety of reasons. Advanced maternal age, traditionally defined as age more than 35 years, has been associated with increased obstetric morbidity and interventions. In addition, perinatal complications are reported to be higher in this patient population, although recent data point to a more favorable outcome. This article reviews the available literature with special emphasis on antepartum, intrapartum, and postpartum complications and perinatal outcome.


Cell characterization using a protein-functionalized pore.
We demonstrate a highly-sensitive and label-free method for characterizing cells based on cell-surface receptors. The method involves measuring a current pulse generated when an individual cell passes through an artificial pore. When the pore is functionalized with proteins, specific interactions between a cell-surface marker and the functionalized proteins retard the cell, thus leading to an increased pulse duration that indicates the presence of that specific biomarker. For proof-of-principle, we successfully screened murine erythroleukemia cells based on their CD34 surface marker in both a single and mixed population of cells. Further, we developed a unified constrained statistical model for estimating the ratios of cells in a mixed population. Finally, we demonstrated our ability to screen a small number of cells (hundreds or less) with high accuracy and sensitivity. Overall, our pore-based method is broadly applicable and, in the future, could provide a full range of in vitro cell-based assays.


MPER-specific antibodies induce gp120 shedding and irreversibly neutralize HIV-1.
Interference with virus entry is known to be the principle mechanism of HIV neutralization by antibodies, including 2F5 and 4E10, which bind to the membrane-proximal external region (MPER) of the gp41 envelope protein. However, to date, the precise molecular events underlying neutralization by MPER-specific antibodies remain incompletely understood. In this study, we investigated the capacity of these antibodies to irrevocably sterilize HIV virions. Long-term effects of antibodies on virions can differ, rendering neutralization either reversible or irreversible. MPER-specific antibodies irreversibly neutralize virions, and this capacity is associated with induction of gp120 shedding. Both processes have similar thermodynamic properties and slow kinetics requiring several hours. Antibodies directed to the CD4 binding site, V3 loop, and the MPER can induce gp120 shedding, and shedding activity is detected with high frequency in plasma from patients infected with divergent genetic HIV-1 subtypes. Importantly, as we show in this study, induction of gp120 shedding is closely associated with MPER antibody inhibition, constituting either a primary event leading to virion neutralization or representing an immediate consequence thereof, and thus needs to be factored into the mechanistic processes underlying their activity.


Management of recurrent malignant pleural effusion in the United Kingdom: survey of clinical practice.
Malignant pleural effusions are often symptomatic and tend to recur after simple aspiration. Pleurodesis may prevent recurrence of the effusion; many agents and techniques have been described. A questionnaire was sent to 448 clinicians in the United Kingdom to determine how pleurodesis is performed in practice. There was a 56% overall response, with replies from 101 respiratory physicians, 88 general physicians, 29 thoracic surgeons, and 35 general surgeons. General surgeons saw few cases of malignant pleural effusion and rarely performed pleurodesis. A patient with recurrent malignant pleural effusion would usually be managed with pleurodesis by 76 (76%) respiratory physicians, 26 (30%) general physicians, and 23 (81%) thoracic surgeons; a further 29 (33%) general physicians would refer such patients to another specialist. Most medical pleurodesis were performed by junior staff, whereas consultant thoracic surgeons were more likely to be concerned with the procedure. All the thoracic surgeons used an intercostal tube drain, usually with suction. An intercostal tube drain was used routinely by only 54 (54%) of the respiratory physicians and 28 (32%) general physicians. Thoracic surgeons preferred talc for pleurodesis whereas physicians most commonly used tetracycline. The variety of methods in use supports the need for randomised, controlled studies to determine the most effective technique of pleurodesis.


The relationship of IL-6 to hormonal mediators, fuel utilization, and systemic hypermetabolism after surgical trauma.
To define the relationship between inflammatory cytokines, hormonal mediators, alteration of energy substrate and hypermetabolism during the early phase after surgical trauma. A prospective case-control study of 13 patients underwent elective surgery for carcinoma between November 1993 and January 1995. They received parenteral supply of adequate glucose and amino acids through central venous catheter after surgery equally. Inflammatory cytokines such as TNF- alpha, IL-1 and IL-6, stress hormones such as norepinephrine, glucagon and insulin, and fuel utilization and hypermetabolism variables such as resting energy expenditure (REE), CRP, free fatty acid, respiratory quotient, the calculated rates of glucose and fat oxidation using indirect calorimetry were measured serially (the day before operation, the end of surgery, and postoperative day (POD) 1, 2 and 5). TNF- alpha and IL-1 were not detected during the study period. Initial elevation and steady decline of IL-6 concentrations were seen after surgical injury, and this response related significantly to post-operative norepinephrine and glucagon levels throughout the study period, and to insulin levels only at the end of surgery. %REE (REE/BEEHB; basal energy expenditure according to the Harris-Benedict equation) on POD 2 and 5, and all CRP levels after surgery were significantly related to IL-6 levels more than hormone levels. Fuel utilization variables on POD 2 were related to both IL-6 and hormone levels. Initial elevation of IL-6 concentration might induce stress hormones such as norepinephrine and glucagon, but not insulin after surgical trauma. Moreover not only hormonal mediators but also cytokine such as IL-6 are responsible for the development of the stress response of the alteration of energy substrate and hypermetabolism.


Wild pollinator activity negatively related to honey bee colony densities in urban context.
As pollinator decline is increasingly reported in natural and agricultural environments, cities are perceived as shelters for pollinators because of low pesticide exposure and high floral diversity throughout the year. This has led to the development of environmental policies supporting pollinators in urban areas. However, policies are often restricted to the promotion of honey bee colony installations, which resulted in a strong increase in apiary numbers in cities. Recently, competition for floral resources between wild pollinators and honey bees has been highlighted in semi-natural contexts, but whether urban beekeeping could impact wild pollinators remains unknown. Here, we show that in the city of Paris (France), wild pollinator visitation rates are negatively correlated to honey bee colony densities present in the surrounding landscape (500m -slope = -0.614; p = 0.001 -and 1000m -slope = -0.489; p = 0.005). Regarding the morphological groups of wild pollinators, large solitary bee and beetle visitation rates were negatively affected by honey bee colony densities within a 500m buffer (slope = -0.425, p = 0.007 and slope = - 0.671, p = 0.002, respectively) and bumblebee visitation rates were negatively affected by honey bee colony density within a 1000m buffer (slope = - 0.451, p = 0.012). Further, lower interaction evenness in plant-pollinator networks was observed with high honey bee colony density within a 1000m buffer (slope = -0.487, p = 0.008). Finally, honey bees tended to focus their foraging activity on managed rather than wild plant species (student t-test, p = 0.001) whereas wild pollinators equally visited managed and wild species. We advocate responsible practices mitigating the introduction of high density of honey bee colonies in urban environments. Further studies are however needed to deepen our knowledge about the potential negative interactions between wild and domesticated pollinators.


Human face recognition ability is specific and highly heritable.
Compared with notable successes in the genetics of basic sensory transduction, progress on the genetics of higher level perception and cognition has been limited. We propose that investigating specific cognitive abilities with well-defined neural substrates, such as face recognition, may yield additional insights. In a twin study of face recognition, we found that the correlation of scores between monozygotic twins (0.70) was more than double the dizygotic twin correlation (0.29), evidence for a high genetic contribution to face recognition ability. Low correlations between face recognition scores and visual and verbal recognition scores indicate that both face recognition ability itself and its genetic basis are largely attributable to face-specific mechanisms. The present results therefore identify an unusual phenomenon: a highly specific cognitive ability that is highly heritable. Our results establish a clear genetic basis for face recognition, opening this intensively studied and socially advantageous cognitive trait to genetic investigation.


Comparative proteomics reveal characteristics of life-history transitions in a social insect.
Honey bee (Apis mellifera) workers are characterized by complex social behavior. Their life-history is dominated by a period of within-nest activity followed by a phase of long-distance flights and foraging. General insights into insect metabolism imply that foraging onset is associated with fundamental metabolic changes, and theory on social evolution suggests metabolic adaptations that are advantageous for the colony as a whole. Here we address the life-history characteristics of workers with LC-MS/MS based relative quantification of major proteins. Our approach includes: i. Calculation of a false positive rate for the identifications, ii. Support of relative protein quantification results obtained from spectral count by non-parametric statistics, and iii. Correction for Type 1 error inflation using a bootstrap iteration analysis. Our data are consistent with the use of glucose as the main fuel for honey bee flight. Moreover, the data delivers information on the expression of ATPsynthases/ATPases, and provide new insights into nurse- and forager-specific patterns of protection against oxidative stress. The results show the suitability of this approach to investigate fundamental biochemical changes in an insect, and provide new evidence for metabolic specializations that occur during the social ontogeny of worker honey bees.


Discrete Green's methods and their application to two-dimensional phase unwrapping.
A fully self-contained discrete framework with discrete equivalents of Stokes's, Gauss's, and Green's theorems is presented. The formulation is analogous to that of continuous operators, but totally discrete in nature, and the exact relationships derived are shown to hold provided that a set of predefined rules is followed in building discrete contours and domains. The method allows for an analytical rigor that is not guaranteed if one translates the classical continuous formulations onto a discretized approximated framework. We clarify several issues related to the use of discrete operators, which may play a crucial role in specific applications such as the two-dimensional phase-unwrapping problem, chosen as our main application example, and we show that reconstruction on irregular domains and/or in the presence of undersampling and noise is better formulated in the discrete framework than in the continuous domain.


The developmental origins of sarcopenia: using peripheral quantitative computed tomography to assess muscle size in older people.
A number of studies have shown strong graded positive relationships between size at birth, grip strength, and estimates of muscle mass in older people. However no studies to date have included direct measures of muscle size. We studied 313 men and 318 women born in Hertfordshire, United Kingdom between 1931 and 1939 who were still resident there and had historical records of growth in early life. Information on lifestyle was collected, and participants underwent peripheral quantitative computed tomography to directly measure forearm and calf muscle size. Birth weight was positively related to forearm muscle area in the men (r = 0.24, p <.0001) and women (r = 0.17, p =.003). There were similar but weaker associations between birth weight and calf muscle area in the men (r = 0.13, p =.03) and in the women (r = 0.17, p =.004). These relationships were all attenuated by adjustment for adult size. We present first evidence that directly measured muscle size in older men and women is associated with size at birth. This may reflect tracking of muscle size and is important because it suggests that benefit may be gained from taking a life course approach both to understanding the etiology of sarcopenia and to developing effective interventions.


Human fucci pancreatic Beta cell lines: new tools to study Beta cell cycle and terminal differentiation.
Regulation of cell cycle in beta cells is poorly understood, especially in humans. We exploited here the recently described human pancreatic beta cell line EndoC-βH2 to set up experimental systems for cell cycle studies. We derived 2 populations from EndoC-βH2 cells that stably harbor the 2 genes encoding the Fucci fluorescent indicators of cell cycle, either from two vectors, or from a unique bicistronic vector. In proliferating non-synchronized cells, the 2 Fucci indicators revealed cells in the expected phases of cell cycle, with orange and green cells being in G1 and S/G2/M cells, respectively, and allowed the sorting of cells in different substeps of G1. The Fucci indicators also faithfully red out alterations in human beta cell proliferative activity since a mitogen-rich medium decreased the proportion of orange cells and inflated the green population, while reciprocal changes were observed when cells were induced to cease proliferation and increased expression of some beta cell genes. In the last situation, acquisition of a more differentiated beta cell phenotype correlates with an increased intensity in orange fluorescence. Hence Fucci beta cell lines provide new tools to address important questions regarding human beta cell cycle and differentiation.


[Diagnostics of congenital cytomegalovirus in Denmark].
Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital malformations in Denmark. The disease is not notifiable, and there are no national data. A regional Danish prospective study from the 1970s found a cCMV incidence of 0.4%. We propose three algorithms for microbiological diagnosing: 1) Testing of pregnant women should only be -applied, when symptoms compatible with CMV infection are present, and no other diagnoses are found. 2) In children less than three weeks of age urine is the -preferred sample. 3) Retrospectively, cCMV may be diagnosed on dried blood spots, if the mother is CMV IgG-positive.


Web alert.
A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Chemical Biology.


Type 1 GM1 gangliosidosis with basal ganglia calcification: a case report.
This report concerns a 10-month-old boy, admitted to the Veterans General Hospital-Kaohsiung with generalized tonic convulsion and aspiration pneumonia. He was found to have had developmental regression, progressive hypotonia and hepatosplenomegaly since four months of age. Physical examination revealed a large head circumference (97th percentile), frontal bossing, depressed nasal bridge, hepatosplenomegaly, broad hands and short fingers. Neurologic examination showed poor control of eye movement, profound hypotonia, muscle weakness, brisk deep tendon reflexes and Babinski's sign. Hypoplasia of the vertebral bodies with anterior beaking, wedge-shaped metacarpals, spatulated ribs and a J-shaped sella turcica were displayed on bone radiographs. Cranial computerized tomography scans showed diffuse brain atrophy, dilated ventricles and calcification of the bilateral basal ganglia. Vacuolated lymphocytes were noted in a peripheral blood smear. Type 1 GM1 gangliosidosis was diagnosed based on a deficiency of beta-galactosidase activity. To our knowledge, basal ganglia calcification in type 1 GM1 gangliosidosis has never been reported in the literature. We suggest that type 1 GM1 gangliosidosis be considered in the differential diagnosis of patients with an early onset of neurologic decline, organomegaly and basal ganglia calcification.


All-or-none craniorachischisis in Loop-tail mutant mouse chimeras.
Mouse embryos homozygous for the mutant gene Loop-tail (Lp) are characterized by craniorachischisis, an open neural tube extending from the midbrain to the tail. In the present study, experimental chimeric mice containing mixtures of genetically mutant (from Lp/+ x Lp/+ matings) and genetically normal cells were produced. Our aim was to determine whether a 'rescue,' phenotypic gradient, or intermediate expression (i.e. alternating areas of open and closed neural tube) would be observed in these chimeras. We report our analyses of Loop-tail mutant chimeras (n = 82) by gross examination, progeny testing and quantitative analysis of glucose phosphate isomerase (GPI) isozyme levels. An all-or-none craniorachischisis in Loop-tail mutant chimeras was observed. Two multicolored adult chimeras, without any gross evidence of a neural tube defect, were shown to be homozygous Loop-tail chimeras (Lp/Lp in equilibrium +/+) by progeny testing. These results indicate that the normal phenotype can be expressed in the presence of mutant cells. Conversely, six neonates with craniorachischisis were shown to be chimeras by GPI analyses. These results show that the full mutant phenotype can be expressed even when one-third to one-half of the cells are genotypically wild-type. This study did not determine which tissue is primarily responsible for the defective neurulation in this mutant, but suggests that a 'threshold' mechanism underlies the Loop-tail mutant phenotype. In some chimeras that threshold is not reached and the neural tube remains open, whereas in other chimeras the threshold is reached and the neural tube closes completely.


Interferon-gamma conditioning ex vivo generates CD25+CD62L+Foxp3+ regulatory T cells that prevent allograft rejection: potential avenues for cellular therapy.
Regulatory T cells (Treg) play important roles in preventing autoimmunity, graft-versus host disease and transplant rejection. In rodent transplant models, tolerance induction strategies can induce graft protective CD25CD4 Treg in vivo but therapeutic exploitation of active regulation will more likely depend on protocols that allow generation or selection of regulatory cells ex vivo for use as a cellular therapy. We have used adoptive transfer skin and islet allograft models to identify, develop and evaluate ex vivo protocols that generate donor-reactive, adaptive Treg. Naïve CDA CD4 T cells were stimulated with allogeneic antigen-presenting cell under neutral conditions or with cytokine modification, restimulated under identical conditions and subsequently analyzed for cytokine profile, phenotypic markers characteristic of Treg and in vivo regulatory function. Without modification, CD4 T cells default to a Th2 phenotype characterized by a dominant interleukin-4 response which is profoundly detrimental to allograft survival. However, addition of exogenous interferon-gamma suppresses interleukin-4 production without priming for effector function, induces suppressor of cytokine signaling-1 and results in up-regulation of Foxp3 and CD62L. The generation of these populations is enhanced by, but is independent of, the presence of naturally occurring endogenous Treg. Most importantly, when tested for regulatory function in vivo, these cells prevent rejection of both skin and islet allografts mediated by effector T cells. These data reveal an unexpected role for interferon-gamma in the generation of Treg ex vivo and suggest a possible route for the generation of regulatory cells for therapeutic use.


Prevalence of Legionella in pharyngeal secretions of patients with pharyngitis.
A serological investigation has suggested that Legionella pneumophila may be associated with sore throat in adults. In a study of 177 adults and children with acute pharyngitis, Legionella species were not isolated from pharyngeal cultures, which utilized selective and nonselective buffered charcoal-yeast extract media. Group A beta-hemolytic streptococci were isolated from 14 percent of the 177 symptomatic patients. Throat cultures from 88 asymptomatic control subjects were negative for Legionella and beta-hemolytic streptococci. Further studies are needed to determine if Legionella species are associated with acute pharyngitis.


Differences in medical care and disease outcomes among black and white women with heart disease.
The risk of cardiovascular mortality is higher among black women than white women, and the reasons for this disparity are largely unexplored. We sought to evaluate differences in medical care and clinical outcomes among black and white women with established coronary artery disease. Among the 2699 women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS), we used Cox proportional hazards models to determine the association of race with risk of coronary heart disease (CHD) events independent of major cardiovascular risk factors or medical therapies. During an average of 4.1 years of follow-up, CHD events were twice as likely in black compared with white women (6.4 versus 3.1 per 100 person-years, hazard ratio, 2.1; 95% confidence interval, 1.5 to 2.8; P<0.001). Black women had higher rates of hypertension, diabetes, and hypercholesterolemia, yet were less likely to receive aspirin or statins. Black women less often had optimal blood pressure (56% versus 63%; P=0.01) and LDL cholesterol (30% versus 38%; P=0.04) control at baseline and during follow-up. After adjusting for these and other differences, black women still had >50% higher CHD event risk (hazard ratio, 1.52; 95% confidence interval, 1.1 to 2.1; P=0.03). In a large cohort of women with heart disease, black women less often received appropriate preventive therapy and adequate risk factor control despite a greater CHD event risk. Interventions to improve appropriate therapy and risk factor control in all women, and especially black women, are needed.


Scope and limitations of absolute configuration determination of allenic natural products using the CCC stretching VCD signal.
The allene functional group in natural products isolated so far exists in a non-racemic form, but its axial chirality is difficult to elucidate. Allenes exhibit a characteristic antisymmetric CCC stretching mode at around 1950 cm-1, and their VCD properties have not been studied in detail. This work, for the first time, applied VCD spectroscopy to allenic natural products and allenic molecules with other asymmetric centers focusing on the antisymmetric CCC stretching mode. This vibrational mode yielded a negligibly weak VCD signal for several molecules, but in the presence of electron-withdrawing and/or conjugating substituents, it generated a stronger one. Its sign was found to be influenced by the nature of substituents. These findings should deepen the understanding of the VCD properties of the allene functional group and should be useful for future studies of chiral allenes.


Scanning for New BRI1 Mutations via TILLING Analysis.
The identification and characterization of a mutational spectrum for a specific protein can help to elucidate its detailed cellular functions. BRASSINOSTEROID INSENSITIVE1 (BRI1), a multidomain transmembrane receptor-like kinase, is a major receptor of brassinosteroids in Arabidopsis (Arabidopsis thaliana). Within the last two decades, over 20 different bri1 mutant alleles have been identified, which helped to determine the significance of each domain within BRI1. To further understand the molecular mechanisms of BRI1, we tried to identify additional alleles via targeted induced local lesions in genomes. Here, we report our identification of 83 new point mutations in BRI1, including nine mutations that exhibit an allelic series of typical bri1 phenotypes, from subtle to severe morphological alterations. We carried out biochemical analyses to investigate possible mechanisms of these mutations in affecting brassinosteroid signaling. A number of interesting mutations have been isolated via this study. For example, bri1-702, the only weak allele identified so far with a mutation in the activation loop, showed reduced autophosphorylation activity. bri1-705, a subtle allele with a mutation in the extracellular portion, disrupts the interaction of BRI1 with its ligand brassinolide and coreceptor BRI1-ASSOCIATED RECEPTOR KINASE1. bri1-706, with a mutation in the extracellular portion, is a subtle defective mutant. Surprisingly, root inhibition analysis indicated that it is largely insensitive to exogenous brassinolide treatment. In this study, we found that bri1-301 possesses kinase activity in vivo, clarifying a previous report arguing that kinase activity may not be necessary for the function of BRI1. These data provide additional insights into our understanding of the early events in the brassinosteroid signaling pathway.


A long lost key opens an ancient lock: Drosophila Myb causes a synthetic multivulval phenotype in nematodes.
The five-protein MuvB core complex is highly conserved in animals. This nuclear complex interacts with RB-family tumor suppressor proteins and E2F-DP transcription factors to form DREAM complexes that repress genes that regulate cell cycle progression and cell fate. The MuvB core complex also interacts with Myb family oncoproteins to form the Myb-MuvB complexes that activate many of the same genes. We show that animal-type Myb genes are present in Bilateria, Cnidaria and Placozoa, the latter including the simplest known animal species. However, bilaterian nematode worms lost their animal-type Myb genes hundreds of millions of years ago. Nevertheless, amino acids in the LIN9 and LIN52 proteins that directly interact with the MuvB-binding domains of human B-Myb and Drosophila Myb are conserved in Caenorhabditiselegans Here, we show that, despite greater than 500 million years since their last common ancestor, the Drosophila melanogaster Myb protein can bind to the nematode LIN9-LIN52 proteins in vitro and can cause a synthetic multivulval (synMuv) phenotype in vivo This phenotype is similar to that caused by loss-of-function mutations in C. elegans synMuvB-class genes including those that encode homologs of the MuvB core, RB, E2F and DP. Furthermore, amino acid substitutions in the MuvB-binding domain of Drosophila Myb that disrupt its functions in vitro and in vivo also disrupt these activities in C. elegans We speculate that nematodes and other animals may contain another protein that can bind to LIN9 and LIN52 in order to activate transcription of genes repressed by DREAM complexes.


Lipid status after pancreas-kidney transplantation.
This study was performed to determine the net effects of euglycemia, resolution of renal failure, immunosuppressant drugs, and hyperinsulinemia on fasting lipid profiles of patients with renal failure and insulin-dependent diabetes mellitus (IDDM) after combined pancreas-kidney transplantation (PKT). Thirty subjects with IDDM received PKT between April 1989 and October 1990, and all were studied. Mean +/- SE age was 35.2 +/- 1.3 yr; 19 recipients were men, and 11 were women. All had a functioning pancreatic allograft post-PKT. Fasting lipid profiles including total cholesterol (C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-chol), and C/HDL-chol were compared before and after PKT (38-555 days divided into groups: preoperation and 0-2, 3-8, and 9-19 mo). Significant hyperlipidemia was observed preoperatively (means +/- SE): C, 5.92 +/- 0.27 mM; HDL-chol, 1.07 +/- 0.09 mM; TG, 5.85 +/- 0.56 mM; and C/HDL-chol, 6.49 +/- 0.83. All lipids and C/HDL-chol dropped immediately after PKT (0-2 mo vs. preoperation, all P less than 0.01, except HDL-chol). After this immediate postoperative period, C, HDL-chol, and TG stabilized at new concentrations. C (5.44 +/- 0.22 mM) and TG (4.54 +/- 0.48 mM) levels were less than preoperation (not statistically significant and P less than 0.05, respectively). HDL-chol was greater than preoperative values (1.29 +/- 0.06 mM, P less than 0.05). C/HDL-chol dropped after PKT (0-2 mo, 4.85 +/- 0.18, P less than 0.01) and continued to decrease throughout the observation period (3-8 mo, 4.42 +/- 0.23; 9-19 mo, 4.23 +/- 0.23; both P less than 0.01 vs. preoperation). There was no statistical difference between lipid concentrations in male and female subjects. The lipid status of subjects with IDDM and renal failure was abnormal before PKT and once lipid concentrations stabilized after PKT (greater than 2 mo), HDL-chol was higher and TG and C/HDL-chol levels were significantly lower than preoperative values. If these changes are sustained, risk of future cardiovascular disease in this group of patients might be significantly reduced.