Estrogen treatment of acetic acid burns to the vagina, cervix, and perineum: a case report and review of the literature.
In colposcopic evaluation of the cervix, acetic acid of 3 to 5% is commonly used for identification of preneoplastic and neoplastic cells. Acetic acid is a known caustic substance and has the potential to cause irritation and chemical burns when there is sufficient concentration or duration of contact. The authors present a unique case of a woman who inadvertently received undiluted acetic acid during a routine colposcopy, resulting in significant chemical burns of the vagina, cervix, and perineum. Her burns were treated with topical estrogen cream of 1 g twice daily applied directly to the wounds. The burn wounds were fully healed within 8 weeks without complication or additional treatment. At 6 months after the injury, the patient was allowed to engage in sexual activity, and vaginal dilation and pelvic floor therapy were initiated. At 12 months postinjury, her only symptomatic scarring at the left vaginal wall continues to improve. Thus, topical estrogen treatment of 1 g applied twice daily should be continued until burn scar maturation is complete and treatment improvement plateaus in cases of burns to the vagina, cervix, and perineum. This case is further clinical evidence of estrogen's positive effect on wound healing and its potential role in burn treatment.


Reconstituted high-density lipoproteins with a disulfide-linked apolipoprotein A-I dimer: evidence for restricted particle size heterogeneity.
The apolipoprotein A-IMilano (apoA-IM) is a molecular variant of apoA-I characterized by the Arg173-->Cys substitution, resulting in the formation of homodimers (A-IM/A-IM) and heterodimers with apoA-II. In order to examine the effects of the introduction of an interchain disulfide bridge on the lipid-binding properties of apoA-I, the present studies compare the kinetics of association of A-IM/A-IM and apoA-I with dimyristoylphosphatidylcholine (DMPC), and the structure and properties of reconstituted HDL containing palmitoyloleoylphosphatidylcholine (POPC) and either A-IM/A-IM or apoA-I. The results show that apoA-I dimerization does not affect the rate of association with DMPC. Apolipoprotein-POPC complexes instead, when analyzed by nondenaturing gradient gel electrophoresis, demonstrate that, differently from apoA-I, A-IM/A-IM forms only two species of rHDL particles despite a wide range of initial lipid to protein ratios. These two rHDL species contain one or two A-IM/A-IM molecules and have a diameter of 7.8 nm and 12.5 nm. Investigations of the A-IM/A-IM structure in these two rHDL, by circular dichroism, fluorescence, and second-derivative UV spectroscopy, suggest that the secondary and tertiary structures of A-IM/A-IM are remarkably similar in both small and large particles. These results suggest that the introduction of an interchain disulfide bridge does not affect the association of apoA-I with lipids but restricts HDL particle size heterogeneity, thus possibly affecting HDL function in lipid metabolism and atherosclerosis protection.


Histone deacetylase-targeted treatment restores retinoic acid signaling and differentiation in acute myeloid leukemia.
Histone deacetylase (HDAC)-dependent transcriptional repression of the retinoic acid (RA)-signaling pathway underlies the differentiation block of acute promyelocytic leukemia. RA treatment relieves transcriptional repression and triggers differentiation of acute promyelocytic leukemia blasts, leading to disease remission. We report that transcriptional repression of RA signaling is a common mechanism in acute myeloid leukemias (AMLs). HDAC inhibitors restored RA-dependent transcriptional activation and triggered terminal differentiation of primary blasts from 23 AML patients. Accordingly, we show that AML1/ETO, the commonest AML-associated fusion protein, is an HDAC-dependent repressor of RA signaling. These findings relate alteration of the RA pathway to myeloid leukemogenesis and underscore the potential of transcriptional/differentiation therapy in AML.


Cervical Cancer Screening Access for Women Who Experience Imprisonment in Ontario, Canada.
Women who experience imprisonment have higher rates of cervical cancer. Lack of access to cervical cancer screening in the community or in prison may contribute to increased cervical cancer incidence. To determine cervical cancer screening rates for women in provincial prison in Ontario, Canada, and to compare these data with data for the general population. This retrospective cohort study used correctional and health administrative data from January 1, 2006, to December 31, 2013. Participants included Ontario women aged 21 to 69 years during the follow-up period with no history of cervical cancer or hysterectomy. Analyses were conducted between July 2017 and September 2018. Women admitted to Ontario provincial prison in 2009 or 2010 and released in 2010 were considered exposed, and women in the general population of Ontario were considered unexposed. Whether women were overdue for cervical cancer screening at the time of admission to prison or on July 1, 2010, for the general population, defined as not having been screened in the previous 3 years, and whether women who were overdue were still overdue after 3 years. There were 4553 women in the prison group and 3 647 936 women in the general population group. The median (interquartile range) age was 36 (29-43) years in the prison group and 43 (34-53) years in the general population. Women in the prison group had 2.20 times (95% CI, 2.08-2.33) the odds of being overdue for cervical cancer screening compared with women in the general population after adjusting for neighborhood income quintile, at 53.9% (95% CI, 51.8%-56.1%) compared with 32.9% (95% CI, 32.8%-33.0%) (P < .001). Women in the prison group also had nearly twice the odds of still being overdue at 3 years, with an odds ratio of 1.87 (95% CI, 1.76-1.99) after adjusting for neighborhood income quintile, and rates of still being overdue of 36.2% (95% CI, 34.5%-38.0%) compared with 21.9% (95% CI, 21.8%-21.9%) (P < .001). Women who experience imprisonment have worse cervical cancer screening access than women in the general population. Work should be done to promote cervical cancer screening awareness and to improve access to acceptable screening in prison and in the community after prison release.


Ineffectiveness of ¹⁸F-fluorodeoxyglucose positron emission tomography in the evaluation of tumor response after completion of neoadjuvant chemoradiation in esophageal cancer.
To evaluate the role of ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of tumor response after the completion of neoadjuvant chemoradiation (CRT) in patients with locally advanced resectable esophageal cancer. After primary CRT, a noninvasive evaluation of the tumor response could help in the treatment decision to identify patients who may benefit from surgery. Whether FDG-PET provides clinically relevant information remains questionable. Operable patients with locally advanced esophageal cancer (clinically staged T3 N0-1 M0) were enrolled in this prospective study. The complete treatment plan included neoadjuvant CRT (cisplatin + 5-fluorouracil/45 Gy) followed 6 to 8 weeks later by a transthoracic en bloc esophagectomy. Morphological evaluation combined with FDG-PET was performed 2 weeks before the start of CRT and 4 to 6 weeks after the completion of CRT. Intratumoral pre- and posttreatment FDG-standardized uptake values (SUV1, SUV2, percentage change) were assessed. These variables were correlated with pathological and morphologic responses and survival. Investigators were blinded to the FDG-PET results unless they revealed metastatic disease. Of 60 total patients, 46 underwent the complete treatment plan (median age: 60.1 years; adenocarcinoma: 25 patients; squamous cell cancer: 21 patients). A major pathological response occurred in 45.7% of patients and was associated with a favorable outcome (P = 0.057). Neoadjuvant CRT led to a significant reduction in intratumoral FDG-uptake (P < 0.001). No significant association was seen between a pathological response (either complete or major) and the FDG-PET results (P > 0.280). The SUV2 value was correlated with a morphological response and the possibility to perform an R0 resection (P < 0.018; receiver operating characteristic curve analysis: SUV2 threshold = 5.5). No significant association was found between metabolic imaging and recurrence or survival. FDG-PET does not effectively correlate with pathological response and long-term survival in patients with locally advanced esophageal cancer undergoing neoadjuvant CRT followed by surgery. (Registered on the www.e-cancer RECF0350.).


The alteration of intracellular enzymes. II. The relation between the surface and the biological activities of altering agents.
1. The ability of homologous series of alcohols, ketones, and aldehydes to cause alteration of intracellular catalase increases approximately threefold for each methylene group added, thus following Traube's rule. Equiactive concentrations of alcohols (methanol to octanol) varied over a 4,000-fold range, yet the average corresponding surface tension was 42 +/- 2 dynes/cm., that for ketones 43 +/- 2, and for aldehydes (above C(1)) 41 +/- 3. 2. Above C(8) the altering activity of alcohols ceased to follow Traube's rule, and at C(18) was nil. Yet the surface activities of alcohols from nonanol to dodecanol did follow Traube's rule. These two facts show that the interface which is being affected by these agents is not the cell surface, for if it were, altering activity should not fall off between C(9) and C(12) where surface activity is undiminished; they show also that micelle formation by short range association of hydrocarbon "tails," usually invoked to explain decrease in biological activity of compounds above C(8), is not responsible for this effect in these experiments, in which permeability of the cell membrane probably is involved. 3. The most soluble alcohols and aldehydes (alcohols C(1) to C(8); aldehydes C(1), C(2)), but not ketones, cause, above optimal concentration, an irreversible inhibition of yeast catalase. 4. The critical concentration of altering agent (i.e., that concentration just sufficient to cause doubling of the catalase activity of the yeast suspension) was independent of the concentration of the yeast cells. 5. Viability studies show that the number of yeast cells killed by the altering agents was not related to the degree of activation of the catalase produced. While all the cells were invariably killed by concentrations of altering agent which produced complete activation, all the cells had been killed by concentrations which were insufficient to cause more than 50 per cent maximal activation. Further, the evidence suggested that the catalase may be partially activated by concentrations of altering agent which cause no decrease in viability at all. Hence alteration, unlike death, may not be all-or-none per cell. 6. The fact that the biological criterion being examined was the activation of a water-soluble enzyme rules out the possibility that the reason for the logarithmic increase in altering activity with chain length was increase in concentration of the altering agent in some intracellular fat phase. It is concluded that these surface-active agents cause enzyme alteration by becoming adsorbed at some intracellular interface and thus causing, directly or indirectly, the modification of catalase properties. 7. It is considered that these data support, but do not provide critical proof for, the interfacial hypothesis, which states that catalase is present at the intracellular interface in question, but is desorbed into solution as a consequence of the alteration process.


Alarmin IL-33 acts as an immunoadjuvant to enhance antigen-specific tumor immunity.
Studies of interleukin (IL)-33 reveal a number of pleiotropic properties. Here, we report that IL-33 has immunoadjuvant effects in a human papilloma virus (HPV)-associated model for cancer immunotherapy where cell-mediated immunity is critical for protection. Two biologically active isoforms of IL-33 exist that are full-length or mature, but the ability of either isoform to function as a vaccine adjuvant that influences CD4 T helper 1 or CD8 T-cell immune responses is not defined. We showed that both IL-33 isoforms are capable of enhancing potent antigen-specific effector and memory T-cell immunity in vivo in a DNA vaccine setting. In addition, although both IL-33 isoforms drove robust IFN-γ responses, neither elevated secretion of IL-4 or immunoglobulin E levels. Further, both isoforms augmented vaccine-induced antigen-specific polyfunctional CD4(+) and CD8(+) T-cell responses, with a large proportion of CD8(+) T cells undergoing plurifunctional cytolytic degranulation. Therapeutic studies indicated that vaccination with either IL-33 isoform in conjunction with an HPV DNA vaccine caused rapid and complete regressions in vivo. Moreover, IL-33 could expand the magnitude of antigen-specific CD8(+) T-cell responses and elicit effector-memory CD8(+) T cells. Taken together, our results support the development of these IL-33 isoforms as immunoadjuvants in vaccinations against pathogens, including in the context of antitumor immunotherapy.


Intra- and interspecific variation of the CCR5 gene in higher primates.
We have evaluated the molecular evolution of the chemokine receptor CCR5 in primates. The chemokine receptor CCR5 serves as a major co-receptor for human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection. Knowledge of evolution of the CCR5 molecule and selection on the CCR5 gene may shed light on its functional role. The comparison of differences between intraspecific polymorphisms and interspecific fixed substitutions provides useful information regarding modes of selection during the course of evolution. There is marked polymorphism in the CCR5 gene sequence within different primate species, whereas sequence divergence between different species is small. By using contingency tests, we compared synonymous (SS) and nonsynonymous (NS) CCR5 mutations occurring within and between a broad range of primates. Our results demonstrate that CCR5 evolution did not follow expectations of strict neutrality at the level of the whole gene. The proportion of NS to SS at the intraspecific level was significantly higher than that observed at the interspecific level. These results suggest that most CCR5 NS polymorphisms are slightly deleterious. However, at domains more closely correlated with its known biological functions, there was no obvious evidence to support deviation from neutrality.


Single-Mode Emission in InP Microdisks on Si Using Au Antenna.
An important building block for on-chip photonic applications is a scaled emitter. Whispering gallery mode cavities based on III-Vs on Si allow for small device footprints and lasing with low thresholds. However, multimodal emission and wavelength stability over a wider range of temperature can be challenging. Here, we explore the use of Au nanorod antennae on InP whispering gallery mode lasers on Si for single-mode emission. We show that by proper choice of the antenna size and positioning, we can suppress the side modes of a cavity and achieve single-mode emission over a wide excitation range. We establish emission trends by varying the size of the antenna and show that the far-field radiation pattern differs significantly for devices with and without antenna. Furthermore, the antenna-induced single-mode emission is dominant from room temperature (300 K) down to 200 K, whereas the cavity without an antenna is multimodal and its dominant emission wavelength is highly temperature-dependent.


Understanding the assessment of psychotropic drug harms in clinical trials to improve social workers' role in medication monitoring.
The purpose of this integrative review is to facilitate social work practitioners' understanding of how psychotropic drug harms are assessed in clinical trials and to make specific suggestions for social workers' increased involvement in detecting drug harms in their clients. The authors undertook a comprehensive review of interdisciplinary sources relating to policies, procedures, and evidence of current practices in adverse event assessment in clinical trial research. Results revealed that few guidelines exist for assessing harms in clinical drug research. Current practices consist primarily of asking research trial subjects general, open-ended questions or relying on spontaneous patient reports. These methods produce inconsistent data and are inadequate to fully inform. Meta-analysis of adverse effect rates across studies has further proven difficult and inconclusive. To address some of these limitations, the authors recommend that social workers contribute to a fuller understanding of drug effects by eliciting clients' own views of treatment effects and by monitoring ongoing effects using a concise yet comprehensive treatment emergent effects checklist. Social workers should also support policy initiatives that lessen or remove control over drug testing from pharmaceutical companies.


Simulation and correction of electron images of tilted planar weak-phase samples.
The phase contrast theory describes the transfer of information from a weak-phase object to the image plane of a transmission electron microscope. For a tilted sample where the distance from the focal plane varies continuously across the field of view, the recently introduced Tilted Contrast Imaging Function (TCIF) model provides the mathematical description of this information transfer. Here we expand the TCIF model to account for astigmatism, and present several methods to generate simulated images of tilted samples and compare them to experimental results. We analyze in depth the differences between TCIF and the classical Contrast Transfer Function (CTF) model, which assumes invariant defocus, and discuss how they can affect the interpretation of experimental data. In addition, we apply the TCIF model to simulated test objects in order to explore the performance of techniques that aim to correct the artifacts introduced by the imaging function, and evaluate how well they recover the original information after optimizing the parameters.


[Effects of a Taegyo program on parent-fetal attachment and parenthood in first pregnancy couples].
The purpose of this study was to explore the effects of a Taegyo program on parents-fetal attachment and parenthood in first pregnancy couples (mothers and spouses). The research design was a nonequivalent control group pretest-posttest experiment. Study participants were 52 first pregnancy couples visiting two medium-scale obstetrics and gynecology clinics located in Gwangju. A total of 52 couples were assigned to the experimental group (25 couples) and the control group (27 couples). The experimental couples were provided with a Taegyo program for 4 weeks. Data were analyzed by chi square test, t-test, and ANCOVA using the SPSS program. Post-treatment maternal-fetal attachment, paternal-fetal attachment and motherhood significantly increased in the experimental group as compared to the control group, but post-treatment fatherhood, anxiety, blood pressure and pulse of participants in the experimental group showed no significant difference from those in the control group. From these results, it is suggested that the Taegyo program has beneficial effects in enhancing parent-fetal attachment and motherhood in first pregnancy couples. Therefore, a Taegyo program can be recommended as a nursing intervention program for first pregnancy couples.


Lipid rescue of massive verapamil overdose: a case report.
Massive intentional verapamil overdose is a toxic ingestion which can cause multiorgan system failure and has no currently known antidote. The patient is a 41-year-old Caucasian woman who ingested 19.2 g of sustained release verapamil in a suicide attempt. Our patient became hypotensive requiring three high-dose vasopressors to maintain arterial pressure. She also developed acute respiratory failure, bradycardic ventricular rhythm necessitating continuous transvenous pacing, and anuric renal failure. Our patient was treated with intravenous calcium, bicarbonate, hyperinsulinemic euglycemic therapy and continuous venovenous hemodialysis without success. On the fourth day after hospital admission continuous intravenous lipid therapy was initiated. Within three hours of beginning lipid therapy, our patient's vasopressor requirement decreased by half. Within 24 hours, she was on minimal vasopressor support and regained an underlying junctional rhythm. After three days of lipid infusion, she no longer required inotropic agents to maintain blood pressure or pacing to maintain stable hemodynamics. Intravenous fat emulsion therapy may be an effective antidote for massive verapamil toxicity.


Metabolic engineering of a carbapenem antibiotic synthesis pathway in Escherichia coli.
Carbapenems, a family of β-lactam antibiotics, are among the most powerful bactericidal compounds in clinical use. However, as rational engineering of native carbapenem-producing microbes is not currently possible, the present carbapenem supply relies upon total chemical synthesis of artificial carbapenem derivatives. To enable access to the full diversity of natural carbapenems, we have engineered production of a simple carbapenem antibiotic within Escherichia coli. By increasing concentrations of precursor metabolites and identifying a reducing cofactor of a bottleneck enzyme, we improved productivity by 60-fold over the minimal pathway and surpassed reported titers obtained from carbapenem-producing Streptomyces species. We stabilized E. coli metabolism against antibacterial effects of the carbapenem product by artificially inhibiting membrane synthesis, which further increased antibiotic productivity. As all known naturally occurring carbapenems are derived from a common intermediate, our engineered strain provides a platform for biosynthesis of tailored carbapenem derivatives in a genetically tractable and fast-growing species.


First record of Ixodes (Scaphixodes) caledonicus in the Carpathian Basin and first time molecular-phylogenetic analysis of this tick species with updated host records and geographical range.
Four Ixodes species represent the subgenus Scaphixodes Schulze, 1941 in Europe, but none of them were reported to be compared in a molecular-phylogenetic context. This study compensates for this lack of data. A tick larva, morphologically identified as Ixodes (Scaphixodes) caledonicus Nuttall, 1910, was collected from an Alpine swift (Tachymarptis melba) during its nesting period in Transylvania, Romania. Following DNA extraction, PCR analyses and sequencing in part with newly designed primers, three genetic markers of this specimen were amplified and compared to GenBank data, and two were analyzed phylogenetically. Based on sequence comparisons of its mitochondrial cytochrome c oxidase subunit I (cox1) and nuclear 28S rRNA genes I. caledonicus appeared to be closely related to members of the subgenus Pholeoixodes. However, the topology of the concatenated cox1 and 16S rRNA gene phylogenetic tree clearly showed its clustering with Ixodes (Scaphixodes) philipi. In conclusion, I. caledonicus is part of the tick fauna of Romania and is expected to occur also in other countries of the Carpathian Basin where rocky cliffs are available for nesting of swifts and other birds. This is the first species of the subgenus Scaphixodes in Europe, for which the traditional (morphology-based) taxonomic assignment is confirmed by molecular-phylogenetic analyses.


Mapping of the Lassa virus LAMP1 binding site reveals unique determinants not shared by other old world arenaviruses.
Cell entry of many enveloped viruses occurs by engagement with cellular receptors, followed by internalization into endocytic compartments and pH-induced membrane fusion. A previously unnoticed step of receptor switching was found to be critical during cell entry of two devastating human pathogens: Ebola and Lassa viruses. Our recent studies revealed the functional role of receptor switching to LAMP1 for triggering membrane fusion by Lassa virus and showed the involvement of conserved histidines in this switching, suggesting that other viruses from this family may also switch to LAMP1. However, when we investigated viruses that are genetically close to Lassa virus, we discovered that they cannot bind LAMP1. A crystal structure of the receptor-binding module from Morogoro virus revealed structural differences that allowed mapping of the LAMP1 binding site to a unique set of Lassa residues not shared by other viruses in its family, illustrating a key difference in the cell-entry mechanism of Lassa virus that may contribute to its pathogenicity.


Positive and negative strands of HCV-RNA in sera and peripheral blood mononuclear cells of chronically hemodialyzed patients.
Hepatitis C virus (HCV) RNA can be detected in sera and peripheral blood mononuclear cells (PBMC) of patients undergoing chronic hemodialysis. However, the natural course of HCV infection in this group of patients is not fully known. Although the exact mechanism of HCV replication is not completely explained, there is evidence that HCV replicate through synthesis of complementary negative (-) RNA strand, whereas positive (+) RNA strand serves as a template. Thus, the detection of negative HCV-RNA strand can be regarded as a marker of ongoing viral replication. We investigated the prevalence of (+) and (-) strands of HCV-RNAs in sera and PBMC of 45 chronically hemodialyzed patients using PCR methods. We also determined HCV genotypes and their subtypes by Inno-LIPA method. Eight (17.8%) of analyzed patients were anti-HCV positive. In this group, we detected HCV-RNA (+) strands in sera and PBMC in 2 and 4 cases respectively, whereas HCV-RNA (-) ones were found in PBMC of 4 patients. Among the remaining 37 anti-HCV negative patients we found HCV-RNA positive strands in sera and PBMC in 2 and 3 cases respectively, whereas HCV-RNA negative strand was present in PBMC in one of them. Our results indicate that HCV actively replicate in PBMC in chronically hemodialyzed patients. In number of patients HCV-RNAs can be detected only in PBMC without concomitant presence of viremia or anti-HCV in sera. We did not find any correlation between genotypes of HCV and presence of HCV-RNAs strands in PBMC of the patients.


In vitro antibiotic susceptibility of Francisella tularensis isolates from Japan.
The antibiotic susceptibilities of 36 isolates of Japanese Francisella tularensis, an etiological agent of the zoonotic disease tularemia, were analyzed using the E test. All the isolates were susceptible to ciprofloxacin, doxycycline, erythromycin, and gentamicin but resistant to benzylpenicillin and cephalothin. The susceptibility to seven other β-lactams (aztreonam, cefotaxime, cefoxitin, ceftriaxone, cefuroxime, imipenem, and meropenem) varied among the isolates. These findings suggest that the guidelines for the antibiotic treatment of tularemia issued by the World Health Organization are appropriate for Japanese tularemia patients.


Preliminary evaluation of PTSD Coach, a smartphone app for post-traumatic stress symptoms.
PTSD Coach is a mobile application (app) designed to help individuals who have post-traumatic stress disorder (PTSD) symptoms better understand and self-manage their symptoms. It has wide-scale use (over 130,000 downloads in 78 countries) and very favorable reviews but has yet to be evaluated. Therefore, this study examines user satisfaction, perceived helpfulness, and usage patterns of PTSD Coach in a sample of 45 veterans receiving PTSD treatment. After using PTSD Coach for several days, participants completed a survey of satisfaction and perceived helpfulness and focus groups exploring app use and benefit from use. Data indicate that participants were very satisfied with PTSD Coach and perceived it as being moderately to very helpful with their PTSD symptoms. Analysis of focus group data resulted in several categories of app use: to manage acute distress and PTSD symptoms, at scheduled times, and to help with sleep. These findings offer preliminary support for the acceptability and perceived helpfulness of PTSD Coach and suggest that it has potential to be an effective self-management tool for PTSD. Although promising, future research is required to validate this, given study limitations.


Knowledge, Attitudes, and Practices Related to Dietary Supplementation, before and during the COVID-19 Pandemic: Findings from a Cross-Sectional Survey in the Lebanese Population.
At the start of 2020, a new coronavirus (COVID-19) invaded the world leading to the death of 3.92 million people. Sadly, to date, no remedy has been discovered for this virus. Preventive vaccines have been under investigation, but were unavailable until December 2020. Clinical deficiencies of nutrients may increase susceptibility to infections. This knowledge may have provided an incentive for some dietary supplement (DS) manufacturers to advertise their products as COVID-19 preventatives or cures without any substantiation, targeting mainly social media fans. The objective of this research was to assess the usage, knowledge and attitudes towards dietary supplementation before and during the COVID-19 pandemic among Lebanese people. A cross-sectional study was conducted based on a convenience sample (N = 2966) and information from participants aged 18 years and above was collected about periods before and during the pandemic. Our findings showed that attitudes towards DSs changed when the pandemic emerged and people believed that DSs can improve their health and strengthen their immunity. Despite the rise in DS prescription by healthcare professionals, the prevalence of DS use decreased from 73.3% before the pandemic to 69.9% during the pandemic (p < 0.001). Study results declared that the weekly or the daily estimated intake had increased during the pandemic as compared to before the pandemic, from 14% to 15.6% for antioxidants (p = 0.014), from 35.3% to 42.1% for vitamin C (p < 0.001), from 35.5% to 41% for vitamin D (p < 0.001), from 15.2% to 17.5% for vitamin E (p = 0.002), and from 18.8% to 29.3% for zinc (p < 0.001) and other vitamins and minerals (from 9% to 10.9%, p < 0.001). Binary logistic regression indicated that the use of DSs during the pandemic was 4 times higher among those infected with COVID-19, 30 times higher among those who used to take DSs before pandemic, and 1.5 times higher among those who worked in the medical sector. To conclude, there is a crucial need to increase awareness among Lebanese people regarding the use of DSs.


MDWiZ: a platform for the automated translation of molecular dynamics simulations.
A variety of popular molecular dynamics (MD) simulation packages were independently developed in the last decades to reach diverse scientific goals. However, such non-coordinated development of software, force fields, and analysis tools for molecular simulations gave rise to an array of software formats and arbitrary conventions for routine preparation and analysis of simulation input and output data. Different formats and/or parameter definitions are used at each stage of the modeling process despite largely contain redundant information between alternative software tools. Such Babel of languages that cannot be easily and univocally translated one into another poses one of the major technical obstacles to the preparation, translation, and comparison of molecular simulation data that users face on a daily basis. Here, we present the MDWiZ platform, a freely accessed online portal designed to aid the fast and reliable preparation and conversion of file formats that allows researchers to reproduce or generate data from MD simulations using different setups, including force fields and models with different underlying potential forms. The general structure of MDWiZ is presented, the features of version 1.0 are detailed, and an extensive validation based on GROMACS to LAMMPS conversion is presented. We believe that MDWiZ will be largely useful to the molecular dynamics community. Such fast format and force field exchange for a given system allows tailoring the chosen system to a given computer platform and/or taking advantage of a specific capabilities offered by different software engines.


[Anxiety and physical limitation: a complex relation].
Psychological problems affecting physically handicapped individuals are understudied. However, some studies suggest a higher risk of developing an elevated level of anxiety among these individuals. A previous study reported that people with multiple sclerosis show more anxiety than patients suffering from another type of physical limitations. These results raise questions about the specificity of the link between anxiety and some medical conditions. The aim of the present study is to increase our understanding of manifestations of anxiety associated with degenerative illnesses. Three groups of patients with different physical limitations were compared on their level of anxiety and on various cognitive process. Groups were composed as: 1) 20 patients suffering from multiple sclerosis, 2) 18 patients diagnosed with another degenerative illness (either arthritis, muscular dystrophy or ataxia), and 3) 20 participants presenting a non-degenerative handicap. The 3 groups were not significantly different on age, sex and duration of the physical limitations. Symptoms of anxiety were measured with 3 questionnaires:1) the Hospital Anxiety and Depression Scale, 2) the Penn State Worry Questionnaire, used to assess the tendency to worry, and 3) the Worry Domains Questionnaire, assessing diversity and intensivity of worry themes. In turn, cognitive processes were evaluated with 4 questionnaires: 1) the Acceptance of Disability scale, used to assess the person's level of acceptance regarding a disability, 2) the Interpretation of Disturbing Thoughts questionnaire, an idiographical measure about the interpretation of thoughts associated with a physical handicap, 3) the Intolerance of Uncertainty scale, presenting beliefs about uncertainty and its consequences, and 4) the Cognitive Avoidance questionnaire, to evaluate the tendency of avoiding disturbing thoughts and images. Participants completed all questionnaires alone and the experimenter was available to answer any questions. MANOVAs were used to compare the 3 groups on the studied variables. Statistical analysis revealed no significant differences among groups for symptoms of anxiety and depression, tendency to worry and worry themes. Similarly, no significant differences were obtained on cognitive processes. The multiple sclerosis group and the other degenerative illness group were combined and compared to the non-degenerative handicap group. MANOVAs conducted on symptoms and cognitive processes did not yield any significant differences. Results of the present study seem to indicate that the type of physical limitations is not an indicator of the presence of specific anxiety symptoms or cognitive processes. On an exploratory basis, all participants were compared according to their level of acceptance of disability. Results indicated that a lower level of acceptance was significantly associated with more anxious and depressive symptoms, excessive worries, and a greater intolerance of uncertainty. It seems that acceptance of disability plays a key role in maintaining psychological distress among people with a physical handicap. The influence of intolerance of uncertainty on acceptance of disability needs to be further explored.


Influence of lysates of the salivary glands of Lutzomyia longipalpis on the development of a Leishmania-major-like parasite in the skin of the golden hamster.
Twelve years ago, some mice inoculated with Leishmania major were found to develop larger lesions, containing more amastigotes, if the inoculum used to infect them contained a lysate of salivary glands from Lutzomyia longipalpis than if no lysate was included. In the present study, outbred golden hamsters (Mesocricetus auratus) were each inoculated in a footpad with 10(4), 10(5), 10(6) or 10(7) stationary-phase promastigotes of a Leishmania-major-like parasite (MHOM/BR/71/BH49). Some of the inocula used each contained a lysate of the salivary glands from a laboratory-reared, female Lu. longipalpis. Only the hamsters inoculated with 10(7) promastigotes each developed macroscopic cutaneous lesions (all 10 co-inoculated with lysate but only two of the 10 co-inoculated with diluent). Each of the lesions developed into cutaneous nodule affecting the dermis and underlying subcutaneous tissue of the inoculated footpad, with, histologically, an intensive, diffuse and productive, inflammatory reaction. There were no apparent differences between the lesions of hamsters infected with inocula containing salivary-gland lysate and those seen in the animals infected with lysate-free inocula. Future studies will follow the histological changes at the sites of Lu. longipalpis bites.


Abnormal aortic valve echoes in mitral prolapse. Echocardiographic features of floppy aortic valve.
The following distinctive combination of M-mode and two dimensional echocardiographic abnormalities of the aortic valve was observed in a group of 12 patients, of whom 11 had mitral valve prolapse. On two dimensional scans, the aortic cusps were freely mobile but appeared thickened or folded. On M-mode records, cusp excursion was normal: there was well defined systolic oscillation, and cusp echoes were multiple and centrally positioned within the aortic root during diastole. The aortic valve was inspected at operation in two patients: a typically myxomatous valve was replaced in one and findings were in keeping with this diagnosis in the other. It is suggested that the echocardiographic features described are characteristic of the floppy aortic valve. Despite the echocardiographic abnormalities, only three patients had clinical evidence of an aortic valve lesion. It is, therefore, further suggested that the investigation of patients with mitral prolapse should include echocardiographic assessment of the aortic valve, even when associated myxomatous degeneration of that valve is not suspected clinically.


Multiple primary malignant neoplasms. A search for an immunogenetic basis.
The occurrence of multiple primary malignant neoplasms in single individuals is well documented. Although many hypotheses have been advanced to explain this occurrence, there has been no study to determine if a presumed "increased susceptibility to cancer" has an immunogenetic basis. We evaluated the cellular immunity and histocompatibility antigens of 42 patients who had had from two to four multiple primary malignant neoplasms. We failed to demonstrate a preexisting impairment of immunocompetence or abnormal HL-A antigen frequencies in these patients. The occurrence of multiple primary malignant neoplasms in related tissues, eg, lung/larynx/oral cavity, and the occurrence of successive primary malignant neoplasms at a time interval consistent with the patient's being cured of preceding malignant neoplasms suggest that multiple primary malignant neoplasms result from repetitive induction by the same or similar etiologic factors in patients who are cured after treatment of the first malignant neoplasm.


"Lives in the balance": The politics of integration in the Partnership for Maternal, Newborn and Child Health.
A decade ago, the Partnership for Maternal, Newborn and Child Health (PMNCH) was established to combat the growing fragmentation of global health action into uncoordinated, issue-specific efforts. Inspired by dominant global public-private partnerships for health, the PMNCH brought together previously competing advocacy coalitions for safe motherhood and child survival and attracted support from major donors, foundations and professional bodies. Today, its founders highlight its achievements in generating priority for 'MNCH', encouraging integrated health systems thinking and demonstrating the value of collaboration in global health endeavours. Against this dominant discourse on the success of the PMNCH, this article shows that rhetoric in support of partnership and integration often masks continued structural drivers and political dynamics that bias the global health field towards vertical goals. Drawing on ethnographic research, this article examines the Safe Motherhood Initiative's evolution into the PMNCH as a response to the competitive forces shaping the current global health field. Despite many successes, the PMNCH has struggled to resolve historically entrenched programmatic and ideological divisions between the maternal and child health advocacy coalitions. For the Safe Motherhood Initiative, the cost of operating within an extremely competitive policy arena has involved a partial renouncement of ambitions to broader social transformations in favour of narrower, but feasible and 'sellable' interventions. A widespread perception that maternal health remains subordinated to child health even within the Partnership has elicited self-protective responses from the safe motherhood contingent. Ironically, however, such responses may accentuate the kind of fragmentation to global health governance, financing and policy solutions that the Partnership was intended to challenge. The article contributes to the emerging critical ethnographic literature on global health initiatives by highlighting how integration may only be possible with a more radical conceptualization of global health governance.


Direct restart of a replication fork stalled by a head-on RNA polymerase.
In vivo studies suggest that replication forks are arrested by encounters with head-on transcription complexes. Yet, the fate of the replisome and RNA polymerase (RNAP) after a head-on collision is unknown. We found that the Escherichia coli replisome stalls upon collision with a head-on transcription complex, but instead of collapsing, the replication fork remains highly stable and eventually resumes elongation after displacing the RNAP from DNA. We also found that the transcription-repair coupling factor Mfd promotes direct restart of the fork after the collision by facilitating displacement of the RNAP. These findings demonstrate the intrinsic stability of the replication apparatus and a previously unknown role for the transcription-coupled repair pathway in promoting replication past a RNAP block.


Biodegradation of tetracycline under various conditions and effects on microbial community.
Five hundred tons of antibiotics are consumed yearly in the world. In this study, the biodegradation characteristics of tetracycline (TET) under nitrate-reducing, sulfate-reducing, and methanogenic conditions were determined by batch tests. Also, effects of TET on mixed microbial cultures were revealed by microbiological analysis. In this scope, gas generation and composition, dissolved organic carbon, and electron acceptor concentrations were monitored during 120 days. Additionally, changes on quantities of specific microbial groups were determined by Q-PCR. TET showed non-biodegradable behavior under nitrate- and sulfate-reducing conditions, whereas slightly biodegradable behavior under methanogenic conditions approximately 46 % degradation. The effects of TET on the abundance of mixed culture varied according to taxonomic units. Sulfate-reducing bacteria were inhibited by TET, while archaeal, bacterial, and methanogenic populations were not affected significantly.


Neurotrophic regulation of fibroblast dedifferentiation during limb skeletal regeneration in the axolotl (Ambystoma mexicanum).
The ability of animals to repair tissue damage is widespread and impressive. Among tissues, the repair and remodeling of bone occurs during growth and in response to injury; however, loss of bone above a threshold amount is not regenerated, resulting in a "critical-size defect" (CSD). The development of therapies to replace or regenerate a CSD is a major focus of research in regenerative medicine and tissue engineering. Adult urodeles (salamanders) are unique in their ability to regenerate complex tissues perfectly, yet like mammals do not regenerate a CSD. We report on an experimental model for the regeneration of a CSD in the axolotl (the Excisional Regeneration Model) that allows for the identification of signals to induce fibroblast dedifferentiation and skeletal regeneration. This regenerative response is mediated in part by BMP signaling, as is the case in mammals; however, a complete regenerative response requires the induction of a population of undifferentiated, regeneration-competent cells. These cells can be induced by signaling from limb amputation to generate blastema cells that can be grafted to the wound, as well as by signaling from a nerve and a wound epithelium to induce blastema cells from fibroblasts within the wound environment.


Oncogenic activation in prostate cancer progression and metastasis: Molecular insights and future challenges.
Prostate cancer is a leading cause of death among men in the United States, and currently early diagnosis and appropriate treatment remain key approaches for patient care. Molecularly prostate cancer cells carry multiple perturbations that generate malignant phenotype capable of uncontrolled growth, survival, and invasion-metastasis to other organs. These alterations are acquired both by genetic and epigenetic changes in tumor cells resulting in the activation of growth factor receptors, signaling proteins, kinases, transcription factors and coregulators, and multiple proteases required for the progression of the disease. Recent advances provide novel insights into the molecular functions of these oncogenic activators, implicating potential therapeutic targeting opportunities for the treatment of prostate cancer.


Rates of clinical depression diagnosis, functional impairment, and nursing home placement in coexisting dementia and depression.
Depression is commonly found as a coexisting condition in dementia. An earlier retrospective study by the authors found that patients with coexisting dementia and depression (CDD) were high utilizers of inpatient and nursing home care. The current prospective study was designed to investigate specific factors that might contribute to outcomes such as nursing home placement by examining the detection and course of CDD subjects as compared with subjects with either disorder alone. Eighty-two subjects (N=29 with CDD, N=27 with Depression Alone, and N=26 with Dementia Alone) were recruited and reassessed at 3, 6, and 12 months after baseline assessment. Lower rates of depression detection by treating (non-study) physicians were found in CDD subjects. Only 35% of the CDD group were correctly diagnosed and receiving adequate treatment for their depression. Although the CDD group did not differ in baseline dementia stage or cognitive functioning as compared with the dementia-only group, they had significantly higher levels of functional impairment. CDD subjects used nursing home care at significantly higher rates; nursing home placement correlated significantly with baseline severity of functional impairment and mood measures, but not with other factors, including dementia stage and medical burden. Undetected, untreated, or inadequately treated depression may result in higher rates of nursing home placement in patients with dementia by increasing their functional disability. Aggressive outpatient treatment of depression could improve the course of coexisting dementia and depression.


The apparent critical isotherm for cryoinsult-induced osteonecrotic lesions in emu femoral heads.
Cryoinsult-induced osteonecrosis (ON) in the emu femoral head provides a unique opportunity to systematically explore the pathogenesis of ON in an animal model that progresses to human-like femoral head collapse. Among the various characteristics of cryoinsult, the maximally cold temperature attained is one plausible determinant of tissue necrosis. To identify the critical isotherm required to induce development of ON in the cancellous bone of the emu femoral head, a thermal finite element (FE) model of intraoperative cryoinsults was developed. Thermal material property values of emu cancellous bone were estimated from FE simulations of cryoinsult to emu cadaver femora, by varying model properties until the FE-generated temperatures matched corresponding thermocouple measurements. The resulting FE model, with emu bone-specific thermal properties augmented to include blood flow effects, was then used to study intraoperatively performed in vivo cryoinsults. Comparisons of minimum temperatures attained at FE nodes corresponding to the three-dimensional histologically apparent boundary of the region of ON were made for six experimental cryoinsults. Series-wide, a critical isotherm of 3.5 degrees C best corresponded to the boundary of the osteonecrotic lesions.


The pattern of neutral molecular variation under the background selection model.
Stochastic simulations of the infinite sites model were used to study the behavior of genetic diversity at a neutral locus in a genomic region without recombination, but subject to selection against deleterious alleles maintained by recurrent mutation (background selection). In large populations, the effect of background selection on the number of segregating sites approaches the effect on nucleotide site diversity, i.e., the reduction in genetic variability caused by background selection resembles that caused by a simple reduction in effective population size. We examined, by coalescence-based methods, the power of several tests for the departure from neutral expectation of the frequency spectra of alleles in samples from randomly mating populations (Tajima's, Fu and Li's, and Watterson's tests). All of the tests have low power unless the selection against mutant alleles is extremely weak. In Drosophila, significant Tajima's tests are usually not obtained with empirical data sets from loci in genomic regions with restricted recombination frequencies and that exhibit low genetic diversity. This is consistent with the operation of background selection as opposed to selective sweeps. It remains to be decided whether background selection is sufficient to explain the observed extent of reduction in diversity in regions of restricted recombination.


The consolidation of object and context recognition memory involve different regions of the temporal lobe.
These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory training. Anisomycin infused into perirhinal or insular cortices blocked long-term (24 h), but not short-term (90 min) object recognition memory. Infusions into the hippocampus or amygdala did not impair object recognition memory. Anisomycin infused into the hippocampus blocked long-term, but not short-term object-in-context recognition memory, whereas infusions administered into the perirhinal cortex, insular cortex, or amygdala did not affect object-in-context recognition memory. These results clearly indicate that distinct regions of the temporal lobe are differentially involved in long-term object and object-in-context recognition memory. Whereas perirhinal and insular cortices are required for consolidation of familiar objects, the hippocampus is necessary for consolidation of contextual information of recognition memory. Altogether, these results suggest that temporal lobe structures are differentially involved in recognition memory consolidation.


Management Strategy for Prostate Imaging Reporting and Data System Category 3 Lesions.
Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions present a clinical dilemma due to their uncertain nature, which complicates the development of a definitive management strategy. These lesions have an incidence rate of approximately 22-32%, with clinically significant prostate cancer (csPCa) accounting for about 10-30%. Therefore, a thorough evaluation is warranted. This review highlights the need for radiology peer review, including the confirmation of dynamic contrast-enhanced (DCE) compliance, as the initial step. Additional MRI models such as VERDICT or Tofts need to be verified. Current evidence shows that imaging and clinical indicators can be used for risk stratification of PI-RADS 3 lesions. For low-risk lesions, a safety net monitoring approach involving annual repeat MRI can be employed. In contrast, lesions deemed potentially risky based on prostate-specific antigen density (PSAD), 68 Ga-PSMA PET/CT, MPS, Proclarix, or AI/machine learning models should undergo biopsy. It is recommended to establish a multidisciplinary team that takes into account factors such as age, PSAD, prostate, and lesion size, as well as previous biopsy pathological findings. Combining expert opinions, clinical-imaging indicators, and emerging methods will contribute to the development of management strategies for PI-RADS 3 lesions.


[Blood pressure lowering tripeptides derived from milk protein].
Fermentation of milk by the Lactobacillus helveticus LBK-16H or hydrolysis of casein by protease of Aspergillus oryzae generates the tripeptide casokinines Val-Pro-Pro and Ile-Pro-Pro. These peptides inhibit the kininase II (also known as Angiotensin Converting Enzyme, ACE). Daily intake of these peptides in sufficient amounts in milk, fruit vegetable drinks or pills slightly decreases the blood pressure in hypertensive patients. The currently available milk peptides decrease the blood pressure clearly less than the antihypertensive drugs. They can therefore merely be used for concomitant and safe lifestyle modification during prevention and therapy of hypertension.


Safety and Efficacy of Chitosan-Dextran Hydrogel in the Middle Ear in an Animal Model.
To investigate the efficacy of chitosan-dextran hydrogel (CDH) in preventing postoperative adhesions between the tympanic membrane (TM) and intratympanic structures, and to evaluate its ototoxicity in an animal study. In the first step, ototoxicity was evaluated with 7 male albino guinea pigs (GPs) via auditory brainstem responses (ABR) before and 4 weeks after unilateral intratympanic injection of CDH and saline solution contralaterally. In the second step, 12 GPs underwent bilateral ear surgery. The middle ear (ME) mucosa was abraded, and the cavity was filled with CDH on one side and packed with Gelfoam on the contralateral side. A control group of 6 GPs underwent the same procedure except that no material was applied in the ME. The animals were euthanized at the end of the 7th week, and otomicroscopic findings were noted and the temporal bones harvested for the histologic examination. The findings were scored and compared. There was no statistically significant difference between the pre- and postoperative ABR thresholds. In the otomicroscopic findings, the most prominent difference between the two groups was the presence of retraction of the TM in the Gelfoam group. The histopathologic findings revealed a higher degree of inflammation in the Gelfoam group compared with the CDH group. This study demonstrated that CDH has no ototoxic effects in GPs. Its use as an ME packing material revealed significantly less TM retraction and inflammatory reaction compared with Gelfoam.


Estimating and testing direct genetic effects in directed acyclic graphs using estimating equations.
In genetic association studies, it is important to distinguish direct and indirect genetic effects in order to build truly functional models. For this purpose, we consider a directed acyclic graph setting with genetic variants, primary and intermediate phenotypes, and confounding factors. In order to make valid statistical inference on direct genetic effects on the primary phenotype, it is necessary to consider all potential effects in the graph, and we propose to use the estimating equations method with robust Huber-White sandwich standard errors. We evaluate the proposed causal inference based on estimating equations (CIEE) method and compare it with traditional multiple regression methods, the structural equation modeling method, and sequential G-estimation methods through a simulation study for the analysis of (completely observed) quantitative traits and time-to-event traits subject to censoring as primary phenotypes. The results show that CIEE provides valid estimators and inference by successfully removing the effect of intermediate phenotypes from the primary phenotype and is robust against measured and unmeasured confounding of the indirect effect through observed factors. All other methods except the sequential G-estimation method for quantitative traits fail in some scenarios where their test statistics yield inflated type I errors. In the analysis of the Genetic Analysis Workshop 19 dataset, we estimate and test genetic effects on blood pressure accounting for intermediate gene expression phenotypes. The results show that CIEE can identify genetic variants that would be missed by traditional regression analyses. CIEE is computationally fast, widely applicable to different fields, and available as an R package.


Normative Values for the Short Physical Performance Battery (SPPB) and Their Association With Anthropometric Variables in Older Colombian Adults. The SABE Study, 2015.
Background: The short physical performance battery (SPPB) is a physical performance test of lower extremity function designed for non-disabled older adults. We aimed to establish reference values for community-dwelling Colombian adults aged 60 years or older in terms of (1) the total score; (2) the three subtest scores (walking speed, standing balance performance, and five times sit-to-stand test); and (3) the time to complete the five times sit-to-stand test, s and the walking speed test. Additionally, we sought to explore how much of the variance in the SPPB subtest scores could be explained by anthropometric variables (age, body mass, height, body mass index, and calf circumference). Methods: Participants were men and women aged 60 years or older who participated in the Health and Well-being and Aging Survey in Colombia, 2015. A sample of 4,211 participants (57.3% women) completed the SPPB test, and their anthropometric variables were evaluated. Age-specific percentiles were calculated using the LMS method (3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles). Results: The mean SPPB total score for the entire sample was 8.73 (2.0) points. On average, the total SPPB score was 0.85 points greater in men than in women (p < 0.001). Significant sex differences were observed in all three age groups tested (60-69, 70-79, and 80+ years). In the full sample, our findings suggested that age, body mass, height, body mass index, and calf circumference are significant contributors to walking speed (p < 0.001) after controlling for confounding factors, including ethnicity, socioeconomic status, and urbanicity. Conclusions: Percentile values are of interest to identify target populations for primary prevention and to estimate the proportion of high or low values for SPPB measures in community-dwelling Colombians aged at least 60 years.


Clinicopathologic features of metastasis in nonsentinel lymph nodes of breast carcinoma patients.
In breast carcinoma patients with a positive sentinel lymph node (SN), the value of complete axillary lymph node dissection has been questioned. Multiple published reports have attempted to identify clinicopathologic characteristics of the primary tumor and SN that are associated with an increased likelihood of positive nonsentinel lymph nodes (NSN). Because of differences in lymph node evaluation techniques and limited patient numbers in each study, the authors performed a meta-analysis to assess the regularity and relative strength of association between various characteristics and the risk of NSN metastasis. A MEDLINE search identified 15 candidate studies, 11 of which met the criteria for analysis. General elements of the studies, the pathologic characteristics evaluated, and the results for selected characteristics were compared. Original data were abstracted from each study and used to calculate odds ratios. The Mantel-Haenszel common odds ratios were calculated to determine the relative strength of the associations. Despite methodologic differences, the correlation between positive NSNs and certain pathologic characteristics was found to be remarkably similar among studies. The 5 individual characteristics found to be associated with the highest likelihood of NSN metastasis are SN metastasis > 2 mm in size, extranodal extension in the SN, tumor size > 2 cm, > 1 positive SN, and lymphovascular invasion in the primary tumor. There is general concordance among studies regarding the association between pathologic characteristics and NSN metastasis in breast carcinoma patients with a positive SN. The pooled analysis identified those factors with the strongest associations that should be evaluated routinely in SN specimens and included in prospective databases for the development of a predictive model.


Beta 3-adrenergic agonist up-regulates uncoupling proteins 2 and 3 in skeletal muscle of the mouse.
Chronic stimulation of the beta3-adrenergic receptor (AR) in obese animals resulted in a reduced adiposity associated with an increased expression of thermogenic uncoupling protein (UCP)1 in adipose tissues. In this study, the mRNA expression of newly cloned UCP isoforms (UCP2 and UCP3) were examined in obese yellow KK and C57BL control mice. UCP2 mRNA was found in all tissues examined, with higher levels in adipose tissues and skeletal muscle of the obese mice. UCP3 mRNA was expressed in skeletal muscle, heart and brown adipose tissue similarly in the two mouse strains. Daily injection of a selective beta3-adrenergic agonist, CL316,243 (0.1 mg/kg), for 10 days resulted in a marked reduction of white fat pad weight and 1.8-4.8-fold increase in the mRNA levels of UCP2 and UCP3 in skeletal muscle of obese mice. No noticeable change in the UCP2 and 3 mRNA levels was found in brown and white adipose tissues. It was also found that CL316,243 injection produced a marked and sustained elevation of the plasma free fatty acid level. These results, together with our previous findings of the fatty acid-induced UCP expression in a myocyte cell line in vitro, suggest that the beta3-AR agonist-induced UCP expression in skeletal muscle may be mediated through the elevated plasma free fatty acids. It was also suggested that anti-obesity effect of beta3-AR agonists is attributable to increased thermogenesis not only by UCP1 but also by UCP2 and UCP3.


Prestimulus alpha power signals attention to retrieval.
The human brain is in distinct processing modes at different times. Specifically, a distinction can be made between encoding and retrieval modes, which refer to the brain's state when it is storing new information or searching for old information, respectively. Recent research proposed the idea of a "ready-to-encode" mode, which describes a prestimulus effect in brain activity that signals (external) attention to encoding and predicts subsequent memory performance. Whether there is also a corresponding "ready-to-retrieve" mode in human brain activity is currently unclear. In this study, we examined whether prestimulus oscillations can be linked to (internal) attention to retrieval. We show that task cues to prepare for retrieval (or testing) in comparison with restudy of previously studied vocabulary word pairs led to a significant decrease of prestimulus alpha power just before the onset of word stimuli. Beamformer analysis localized this effect in the right secondary visual cortex (Brodmann area 18). Correlation analysis showed that the task cue-induced, prestimulus alpha power effect is positively related to stimulus-induced alpha/beta power, which in turn predicted participants' memory performance. The results are consistent with the idea that prestimulus alpha power signals internal attention to retrieval, which promotes the elaborative processing of episodic memories. Future research on brain-computer interfaces may find the findings interesting regarding the potential of using online measures of fluctuating alpha oscillations to trigger the presentation and sequencing of restudy and testing trials, ultimately enhancing instructional learning strategies.


Heritability of left ventricular mass: the Framingham Heart Study.
Left ventricular hypertrophy is associated with an increased risk for cardiovascular disease. The known determinants of left ventricular hypertrophy only partially explain its variability. The purpose of this study was to estimate heritability of left ventricular mass. The study sample included adults in the original Framingham Heart Study and the Framingham Offspring Study who were not receiving antihypertensive medications and who were free of coronary heart disease, congestive heart failure, diabetes mellitus, renal insufficiency, valvular heart disease, and severe left ventricular hypertrophy. Intraclass correlations for left ventricular mass among first-degree relatives, second-degree relatives, and unrelated spouse pairs were calculated to determine the contribution of heredity to the variability in left ventricular mass. After adjustments for age, height, weight, and systolic blood pressure, the intraclass correlations between first-degree relatives were .15 (parent-child, P<.001) to .16 (siblings, P<.001), between second-degree relatives the correlation was .06 (P=NS), and between spouses it was .05 (P=NS). The estimated heritability of adjusted left ventricular mass was between .24 and .32. The proportion of the variance in sex-specific left ventricular mass explained by age, height, weight, and systolic blood pressure was .26 in men and .34 in women. On the basis of intraclass correlations for left ventricular mass, incorporation of adjusted left ventricular mass of a parent or sibling would increase the explained variance by an additional .02 to .03. Heredity explains a small, but discernible proportion of the variance in left ventricular mass. Studies are currently under way to identify genetic markers that predict an individual's predisposition to left ventricular hypertrophy. This knowledge may lead to advances in the prevention of left ventricular hypertrophy, which is strongly associated with cardiovascular morbidity and mortality.


The influence of running velocity on resultant tibial acceleration in runners.
Tibial acceleration is a surrogate measure for impact loading and might be useful for identifying lower limb fatigue injury in runners. The resultant tibial acceleration calculated from all three axes of a triaxial accelerometer provides a single metric that is independent of the sensor orientation. The purpose of this study was to investigate the relationship between resultant tibial acceleration and running velocity, and to establish a normative database of tibial acceleration profiles. Triaxial accelerometers were attached to the distal tibiae of 85 runners before they ran on a treadmill for 2 min each, at speeds of 2.7, 3.0, 3.3, and 3.7 m/s. Differences in resultant tibial acceleration were calculated using a one-way ANOVA, and the relationship between tibial acceleration and velocity was determined using a Pearson correlation coefficient and a multiple linear regression analysis. Tibial acceleration increased with higher velocities, with an average increase of 3.8 g (38%) between the slowest and fastest speeds. A moderate correlation was demonstrated between tibial acceleration and running velocity, and 19% of tibial acceleration was explained by velocity. While velocity influences tibial acceleration, individual variances to this relationship exist, highlighting the need for a personalised approach to understanding the response of each runner.


Prevention of knee injuries in sports. A systematic review of the literature.
We reviewed evidence regarding risk factors associated with incidence of knee injuries both to assess the effectiveness of prevention strategies, and to offer evidence-based recommendations to physicians, coaches, trainers, athletes, and researchers. We searched electronic data bases without language restriction for the years 1966 - September 1, 2001, identified citations from reference sections of research papers retrieved, contacted experts in the field, and searched the Cochrane Collaboration. Of the 328 citations identified, we emphasized the results from the 13 reports that compared alternative methods to prevent knee injury and assessed the methodologic quality of these reports using a standardized instrument. Five studies addressed the effectiveness of bracing in football players; these studies showed no consistent evidence of benefit. Two studies comparing alternative cleat designs and a controlled study testing the effects of adjustments in the ski boot/binding system were difficult to interpret because of inadequate reporting of methodology. Six prospective studies that addressed the impact of conditioning and training showed promise of proprioception and neuromuscular training for protection against knee injury. We identified serious flaws in study design, control of bias, and statistical methods; the median quality scores ranged from 11 to 56 (out of 100). Structured training programs that emphasize neuromuscular and proprioceptive training offer encouraging evidence for the prevention of knee injuries. However, flaws in study design and implementation have limited the effectiveness of work in this field. A rigorously implemented research program is needed to address this critically important sports medicine problem.


Genetics of early-onset coronary artery disease: from discovery to clinical translation.
This review is a comprehensive update on recent discoveries on the genetics of early-onset coronary artery disease (EOCAD), and how those findings can be translated to advance its medical management. To date, a total of 266 common variants of modest effect size have been reported to be associated with CAD, but many still warrant functional studies. Rare variants impacting the function of at least 10 genes are now well characterized in Mendelian EOCAD. Estimations of minor allele frequencies in multiple ancestries from large genetic databases have allowed us to estimate the prevalence of Mendelian forms of EOCAD. In fact, the prevalence of Mendelian mutations varies markedly between ancestries, ranging from 1 : 289 to 1 : 153 for familial hypercholesterolemia. Mendelian forms of EOCAD support three major biological pathways, including lipid metabolism, vascular wall integrity and function, and thrombosis. Furthermore, combining common variants of modest effect into polygenic risk scores (PRS) has shown to be effective at identifying individuals at high risk of CAD. Mendelian forms of EOCAD highlight the importance of lipid metabolism, yet prevalence in many non-European populations remains to be clarified. Polygenic EOCAD affects more individuals and, in many cases, confers a higher risk of EOCAD than rare Mendelian mutations. Thus, sequencing of target genes and the derivation of PRSs can be used to identify high-risk patients, leading to more personalized therapeutic approaches.


Reading text increases binocular disparity in dyslexic children.
Children with developmental dyslexia show reading impairment compared to their peers, despite being matched on IQ, socio-economic background, and educational opportunities. The neurological and cognitive basis of dyslexia remains a highly debated topic. Proponents of the magnocellular theory, which postulates abnormalities in the M-stream of the visual pathway cause developmental dyslexia, claim that children with dyslexia have deficient binocular coordination, and this is the underlying cause of developmental dyslexia. We measured binocular coordination during reading and a non-linguistic scanning task in three participant groups: adults, typically developing children, and children with dyslexia. A significant increase in fixation disparity was observed for dyslexic children solely when reading. Our study casts serious doubts on the claims of the magnocellular theory. The exclusivity of increased fixation disparity in dyslexics during reading might be a result of the allocation of inadequate attentional and/or cognitive resources to the reading process, or suboptimal linguistic processing per se.


Cancers Attributable to Infections in the US in 2017: A Meta-Analysis.
Infections are largely modifiable causes of cancer. However, there remains untapped potential for preventing and treating carcinogenic infections in the US. To estimate the percentage and number of incident cancers attributable to infections in the US among adults and children for the most recent year cancer incidence data were available (2017). A literature search from 1946 onward was performed in MEDLINE on January 6, 2023, to obtain the data required to calculate population attributable fractions for 31 infection-cancer pairs. National Health and Nutrition Examination Survey data were used to estimate the population prevalence of hepatitis B and C viruses and Helicobacter pylori. Studies conducted in the US or other Western countries were selected according to specific infection-cancer criteria. Data from 128 studies were meta-analyzed to obtain the magnitude of an infection-cancer association or prevalence of the infection within cancer cells. The proportion of cancer incidence attributable to 8 infections. Of the 1 666 102 cancers diagnosed in 2017 among individuals aged 20 years or older in the US, 71 485 (4.3%; 95% CI, 3.1%-5.3%) were attributable to infections. Human papillomavirus (n = 38 230) was responsible for the most cancers, followed by H pylori (n = 10 624), hepatitis C virus (n = 9006), Epstein-Barr virus (n = 7581), hepatitis B virus (n = 2310), Merkel cell polyomavirus (n = 2000), Kaposi sarcoma-associated herpesvirus (n = 1075), and human T-cell lymphotropic virus type 1 (n = 659). Cancers with the most infection-attributable cases were cervical (human papillomavirus; n = 12 829), gastric (H pylori and Epstein-Barr virus; n = 12 565), oropharynx (human papillomavirus; n = 12 430), and hepatocellular carcinoma (hepatitis B and C viruses; n = 10 017). The burden of infection-attributable cancers as a proportion of total cancer incidence ranged from 9.6% (95% CI, 9.2%-10.0%) for women aged 20 to 34 years to 3.2% (95% CI, 2.4%-3.8%) for women aged 65 years or older and from 6.1% (95% CI, 5.2%-7.0%) for men aged 20 to 34 years to 3.3% (95% CI, 1.9%-4.4%) for men aged 65 years or older. Among those aged 19 years or younger, 2.2% (95% CI, 1.3%-3.0%) of cancers diagnosed in 2017 were attributable to Epstein-Barr virus. Infections were estimated to be responsible for 4.3% of cancers diagnosed among adults in the US in 2017 and, therefore, represent an important target for cancer prevention efforts.


Transcriptional responses in honey bee larvae infected with chalkbrood fungus.
Diseases and other stress factors working synergistically weaken honey bee health and may play a major role in the losses of bee populations in recent years. Among a large number of bee diseases, chalkbrood has been on the rise. We present here the experimental identification of honey bee genes that are differentially expressed in response to infection of honey bee larvae with the chalkbrood fungus, Ascosphaera apis. We used cDNA-AFLP Technology to profile transcripts in infected and uninfected bee larvae. From 64 primer combinations, over 7,400 transcriptionally-derived fragments were obtained A total of 98 reproducible polymorphic cDNA-AFLP fragments were excised and sequenced, followed by quantitative real-time RT-PCR (qRT-PCR) analysis of these and additional samples.We have identified a number of differentially-regulated transcripts that are implicated in general mechanisms of stress adaptation, including energy metabolism and protein transport. One of the most interesting differentially-regulated transcripts is for a chitinase-like enzyme that may be linked to anti-fungal activities in the honey bee larvae, similarly to gut and fat-body specific chitinases found in mosquitoes and the red flour beetle. Surprisingly, we did not find many components of the well-characterized NF-kappaB intracellular signaling pathways to be differentially-regulated using the cDNA-AFLP approach. Therefore, utilizing qRT-PCR, we probed some of the immune related genes to determine whether the lack of up-regulation of their transcripts in our analysis can be attributed to lack of immune activation or to limitations of the cDNA-AFLP approach. Using a combination of cDNA-AFLP and qRT-PCR analyses, we were able to determine several key transcriptional events that constitute the overall effort in the honey bee larvae to fight natural fungal infection. Honey bee transcripts identified in this study are involved in critical functions related to transcriptional regulation, apoptotic degradation of ubiquitinated proteins, nutritional regulation, and RNA processing. We found that immune regulation of the anti-fungal responses in honey bee involves highly coordinated activation of both NF-kappaB signaling pathways, leading to production of anti-microbial peptides. Significantly, activation of immune responses in the infected bee larvae was associated with down-regulation of major storage proteins, leading to depletion of nutritional resources.


Peptoid-directed assembly of CdSe nanoparticles.
The high information content of proteins drives their hierarchical assembly and complex function, including the organization of inorganic nanomaterials. Peptoids offer an organic scaffold very similar to proteins, but with a wider solubility range and easily tunable side chains and functional groups to create a variety of self-assembling architectures with atomic precision. If we could harness this paradigm and understand the factors that govern how they direct nucleation and assembly of inorganic materials to design order within such materials, new dimensions of function and fundamental science would emerge. In this work, peptoid tubes and sheets were explored as platforms to assemble colloidal quantum dots (QDs) and clusters. We have successfully synthesized CdSe QDs with difunctionalized capping ligands containing both carboxylic acid and thiol groups and mixed them with maleimide containing peptoids, to create an assembly of the QDs on the peptoid surface via a covalent linkage. This conjugation was seen to be successful with peptoid tubes, sheets and CdSe QDs and clusters. The particles were seen to have a high preference for the peptoid surface but non-specific interactions with carboxylic acid groups on the peptoids limited control over QD density via maleimide conjugation. Replacing the carboxylic acid groups with methoxy ethers, however, allowed for control over QD density as a function of maleimide concentration. 1H NMR analysis demonstrated that binding of QDs to peptoids involved a subset of surface ligands bound through the carboxylate functional group, allowing the distal thiol to engage in a covalent linkage to the maleimide. Overall, we have shown the compatibility and control of CdSe-peptoid interactions via a covalent linkage with varying peptoid structures and CdSe particles to create complex hybrid structures.


[The mild encephalitis-hypothesis--new findings and studies].
Causes and pathogenesis of psychiatric disorders is poorly understood. Infections by viruses or other agents may disturb neurotransmitters and elicit behavioral abnormalities, and induce long lasting immune reactions, referred to as mild encephalitis (ME). New findings (pathology, biochemistry, imaging) in schizophrenia and bipolar psychoses are compatible with ME hypothesis. In Chorea Sydenham and PANDAS syndrome autoimmune ME seems to explain anxiety-compulsive-hyperactivity symptoms. Add-on-therapy with Cox-II-blockers or valacyclovir improved acute schizophrenia, CSF filtration some cases of therapy resistant psychoses.


Integrating Voice Quality Cues in the Pitch Perception of Speech and Non-speech Utterances.
Pitch perception plays a crucial role in speech processing. Since F0 is highly ambiguous and variable in the speech signal, effective pitch-range perception is important in perceiving the intended linguistic pitch targets. This study argues that the effectiveness of pitch-range perception can be achieved by taking advantage of other signal-internal information that co-varies with F0, such as voice quality cues. This study provides direct perceptual evidence that voice quality cues as an indicator of pitch ranges can effectively affect the pitch-height perception. A series of forced-choice pitch classification experiments with four spectral conditions were conducted to investigate the degree to which manipulating spectral slope affects pitch-height perception. Both non-speech and speech stimuli were investigated. The results suggest that the pitch classification function is significantly shifted under different spectral conditions. Listeners are likely to perceive a higher pitch when the spectrum has higher high-frequency energy (i.e., tenser phonation). The direction of the shift is consistent with the correlation between voice quality and pitch range. Moreover, cue integration is affected by the speech mode, where listeners are more sensitive to relative difference within an utterance when hearing speech stimuli. This study generally supports the hypothesis that voice quality is an important enhancement cue for pitch range.


COMPUTER AIDED EVALUATION OF PLEURAL EFFUSION USING CHEST CT IMAGES.
A pleural effusion is a condition where there is a buildup of abnormal fluid within the pleural space. This paper presents an automated method to evaluate the severity of pleural effusion using regular chest CT images. First the lungs are segmented using region growing, mathematical morphology and anatomical knowledge. Then the visceral and parietal layers of the pleura are extracted based on anatomical landmarks, curve fitting and active contour models. Finally, the pleural space is segmented and the pleural effusion is quantified. Our method was tested on 15 chest CT studies. The automated segmentation is validated against manual tracing and radiologist's qualitative grading. The Pearson correlation between computer evaluation and radiologist's grading is 0.956 (P=10(-7)). The Dice coefficient between the automated and manual segmentation is 0.74±0.07, which is comparable to the variation between two different manual tracings.


pH-Responsive Biomaterials for the Treatment of Dental Caries-A Focussed and Critical Review.
Dental caries is a common and costly multifactorial biofilm disease caused by cariogenic bacteria that ferment carbohydrates to lactic acid, demineralizing the inorganic component of teeth. Therefore, low pH (pH 4.5) is a characteristic signal of the localised carious environment, compared to a healthy oral pH range (6.8 to 7.4). The development of pH-responsive delivery systems that release antibacterial agents in response to low pH has gained attention as a targeted therapy for dental caries. Release is triggered by high levels of acidogenic species and their reduction may select for the establishment of health-associated biofilm communities. Moreover, drug efficacy can be amplified by the modification of the delivery system to target adhesion to the plaque biofilm to extend the retention time of antimicrobial agents in the oral cavity. In this review, recent developments of different pH-responsive nanocarriers and their biofilm targeting mechanisms are discussed. This review critically discusses the current state of the art and innovations in the development and use of smart delivery materials for dental caries treatment. The authors' views for the future of the field are also presented.


Measurement of D-dimer as aid in risk evaluation of VTE in elderly patients hospitalized for acute illness: a prospective, multicenter study in China.
Advanced age and hospitalization are associated with increasing risk of venous thromboembolic (VTE) events. The aim of this study was to investigate whether elevated D-dimer levels could predict VTE events in elderly patients hospitalized for acute illness. 458 consecutive patients (65% men; mean age, 77 ± 7 years) who were older than 60 years, immobilized for ≥ 3 days, and hospitalized for heart failure, respiratory failure, acute ischemic stroke, or acute infectious disease without pharmacological prophylaxis or recent major surgery, were enrolled. Elevated D-dimer levels were defined as > 500 ng/ml. VTE events included symptomatic VTE within 90 days or asymptomatic deep venous thrombosis screened by compression ultrasonography at enrollment and 3-week follow-up. The association between baseline D-dimer levels and subsequent VTE events, adjusted for age, sex, ethnicity, body mass index, co-morbidities, and acute disease status, was assessed using multivariate Cox proportional hazard models. 49.1% (n = 225) of patients had elevated baseline D-dimer levels, and of these patients, 14.2% (n = 32) developed VTE during the 90-day follow-up. In contrast,only 5.6% (n = 13) of patients with normal D-dimer levels developed VTE. Multivariate analysis showed that patients with elevated D-dimer levels had a 3.2-fold increased risk of developing VTE (95% confidence interval, 1.5-6.5; P = 0.002) in comparison with patients with normal levels. In elderly patients who were hospitalized for acute medical illness, elevated D-dimer levels are associated with subsequent VTE events. Our data suggest that measurement of D-dimer, a widely-performed objective test, may help clinicians address high-risk individuals for VTE.


Genomic structure of the human lysosomal alpha-mannosidase gene (MANB).
Lysosomal alpha-mannosidase (LAMAN) (EC 220.127.116.11) is an exoglycosidase involved in the ordered degradation of N-linked oligosaccharides. Lack of LAMAN activity leads to the lysosomal storage disorder alpha-mannosidosis (MIM No. 248500). We determined the genomic organization of the human lysosomal alpha-mannosidase gene (laman; HGMW-approved symbol MANB) by using oligonucleotide primers designed from the human laman cDNA sequence as part of a PCR-based strategy. The gene spanned 21.5 kb and contained 24 exons. By primer extension analysis, the major transcription initiation sites were mapped to positions -309, -196, and -191 relative to the first in-frame ATG. No CAAT or TATA sequences could be identified within 134 bp upstream of the transcription initiation sites, but the 5' flanking region contained several GC-rich regions with putative binding sites for the transcription factors SP-1, AP-2, and ETF.


Prevention of HPV-Related Oral Cancer by Dentists: Assessing the Opinion of Dutch Dental Students.
The aim of this study is to assess dental students' opinions of the dentists' role in primary prevention of human papillomavirus (HPV)-related oral cancer using a cross-sectional web-based survey. A questionnaire, containing questions about knowledge of HPV and oral cancer, confidence in head and neck examination and role of the dentist in preventing HPV-related oral cancer, was sent to all students of the Academic Centre of Dentistry Amsterdam (n = 912). One hundred and twenty-six (n = 126) students completed the questionnaire. Significantly, more master students (75%) than bachelor students (54.3%) were aware that HPV is a causative factor for oral cancer. Master students had more knowledge of HPV than bachelor students, but knowledge about HPV vaccination was irrespective of the study phase. The majority of dental students agreed that it is important to discuss HPV vaccination with patients. Eighty-nine percent of the students think that more education about symptoms of oral cancer will increase screening for oral cancer. Development of a protocol for screening in dental practices was considered even more important. According to dental students, dentists should discuss HPV as a risk factor for oral cancer with patients. Future dentists are willing to be involved in both primary and secondary prevention of HPV-related oral cancer. Therefore, screening for oral cancer and education about HPV vaccination should be integral elements of the dental curriculum.


Comparison Between NIST and AF Laser Energy Standards Using High Power Lasers.
We report the results of a high-energy laser calorimeter comparison conducted by the National Institute of Standards and Technology (NIST), Boulder, Colorado and the U.S. Air Force Primary Standards laboratory (AFPSL), Heath, Ohio. A laser power meter, used as a transfer standard, was calibrated at each laboratory, sequentially, and the measurement results were compared. These measurements were performed at a nominal power of 800 W and a wavelength of 10.6 μm using CO2 lasers. Excellent measurement agreement (1.02 %) was demonstrated, which was well within each of the expanded uncertainties from the two laboratories involved in this comparison.


Diagnostic Performance of MRI, Molecular Breast Imaging, and Contrast-enhanced Mammography in Women with Newly Diagnosed Breast Cancer.
Background Staging newly diagnosed breast cancer by using dynamic contrast material-enhanced MRI is limited by access, high cost, and false-positive findings. The utility of contrast-enhanced mammography (CEM) and 99mTc sestamibi-based molecular breast imaging (MBI) in this setting is largely unknown. Purpose To compare extent-of-disease assessments by using MRI, CEM, and MBI versus pathology in women with breast cancer. Materials and Methods In this HIPAA-compliant prospective study, women with biopsy-proven breast cancer underwent MRI, CEM, and MBI between October 2014 and April 2018. Eight radiologists independently interpreted each examination result prospectively and were blinded to interpretations of findings with the other modalities. Visibility of index malignancies, lesion size, and additional suspicious lesions (malignant or benign) were compared during pathology review. Accuracy of index lesion sizing and detection of additional lesions in women without neoadjuvant chemotherapy were compared. Results A total of 102 women were enrolled and 99 completed the study protocol (mean age, 51 years ± 11 [standard deviation]; range, 32-77 years). Lumpectomy or mastectomy was performed in 71 women (79 index malignancies) without neoadjuvant chemotherapy and in 28 women (31 index malignancies) with neoadjuvant chemotherapy. Of the 110 index malignancies, MRI, CEM, and MBI depicted 102 (93%; 95% confidence interval [CI]: 86%, 97%), 100 (91%; 95% CI: 84%, 96%), and 101 (92%; 95% CI: 85%, 96%) malignancies, respectively. In patients without neoadjuvant chemotherapy, pathologic size of index malignancies was overestimated with all modalities (P = .02). MRI led to overestimation of 24% (17 of 72) of malignancies by more than 1.5 cm compared with 11% (eight of 70) with CEM and 15% (11 of 72) with MBI. MRI depicted more (P = .007) nonindex lesions, with sensitivity similar to that of CEM or MBI, resulting in lower positive predictive value of additional biopsies (13 of 46 [28%; 95% CI: 17%, 44%] for MRI; 14 of 27 [52%; 95% CI: 32%, 71%] for CEM; and 11 of 25 [44%; 95% CI: 24%, 65%] for MBI (overall P = .01). Conclusion Contrast-enhanced mammography, molecular breast imaging, and MRI showed similar detection of all malignancies. MRI depicted more nonindex suspicious benign lesions than did contrast-enhanced mammography or molecular breast imaging, leading to lower positive predictive value of additional biopsies. All three modalities led to overestimation of index tumor size, particularly MRI. © RSNA, 2019 Online supplemental material is available for this article.


A multi-investigator/institutional DNA bank for AIDS-related human genetic studies: AACTG Protocol A5128.
An understanding of the relationships among allelic variability and clinical outcomes will be critical if HIV-infected patients are to benefit from the explosion in knowledge in human genomics. Human DNA banks must allow future analyses while addressing confidentiality, ethical, and regulatory issues. A multidisciplinary group of clinical investigators, ethicists, data managers, regulatory specialists, and community representatives developed Adult AIDS Clinical Trials Group (AACTG) Protocol A5128. Participants in past or present AACTG clinical trials may contribute DNA. Extraction from whole blood is performed at a central laboratory, where participants' unique identifiers are replaced by randomly assigned identifiers prior to DNA storage. To identify genotype-phenotype relationships, genetic assay results can be temporarily linked to clinical trials data. Institutional review boards in 21 states and Puerto Rico have approved Protocol A5128, and accrual is ongoing. Of the first 4,247 enrollees, 82% are male, 56% are white, 26% are African American, and 15% are Hispanic. Because participants may participate in multiple AACTG protocols, these represent 11,424 cases in 324 different AACTG studies and substudies, with at least 100 participants from 24 different studies. Studies exploring specific genotype-phenotype relationships are underway. The AACTG DNA bank will be an important resource for genomic discovery relevant to HIV therapy.


Heterotrimeric Gq proteins as therapeutic targets?
Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein-coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one-third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human disease. Several recent studies have brought to light that the Gq family-specific inhibitor FR900359 (FR) is unexpectedly efficacious in silencing the signaling of Gq oncoproteins, mutant Gq variants that mostly exist in the active state. These data not only raise the hope that researchers working in drug discovery may be able to potentially strike Gq oncoproteins from the list of undruggable targets, but also raise questions as to how FR achieves its therapeutic effect. Here, we place emphasis on these recent studies and explain why they expand our pharmacological armamentarium for targeting Gq protein oncogenes as well as broaden our mechanistic understanding of Gq protein oncogene function. We also highlight how this novel insight impacts the significance and utility of using G(q) proteins as targets in drug discovery efforts.


Pain and load progression following an early maximal strength training program in total hip- and knee arthroplasty patients.
Total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients significantly increase muscle strength after maximal strength training (MST) initiated soon after surgery. Owing to severe postoperative pain, knee patients are anticipated to be more limited in performing heavy load exercises than hip patients. The aim of the present study was to describe pain and load progression during early MST in THA and TKA patients. Explorative study based on secondary analyses from two randomized controlled trials: 26 THA and 16 TKA patients had their training sessions logged. They trained at 85-90% of their maximal capacity in leg press, and abduction/knee-extension of the operated leg (4 × 5 repetitions) for 8-10 weeks, initiated early postoperatively. Knee patients experienced significantly more pain than hip patients during the training sessions (p < 0.03), however, pain before and after training was not different (p > 0.09). All patients significantly increased leg press training load until the last intervention week (p < 0.01). This study demonstrates that TKA patients experience more pain than THA patients during training following a MST program but not more than moderate levels during or after training. Pain before and after training is not different. Both groups significantly increased load progression during the intervention. These findings indicate that both THA and TKA patients might perform MST with extensive load progression early after surgery without compromising pain. The studies were registered at ClinicalTrials.gov .


Decompensated heart failure in the emergency department of a cardiology hospital.
National studies on decompensated heart failure (DHF) are key to the understanding of this condition in our midst. To determine the characteristics of DHF patients in an emergency department. A total of 212 patients diagnosed with decompensated heart failure who had been admitted to an emergency department (EU) of a cardiology hospital were prospectively evaluated. Clinical variables, form of presentation and causes of decompensation were studied. In 100 patients, ancillary tests, prescription of vasoactive drugs, length of hospital stay and mortality were also analyzed. There was a predominance of the male gender (56%) and the most frequent etiology was ischemia (29,7%) despite high frequency of valvular (15%) and chagasic (14,7%) etiologies. The most common form of presentation and cause of decompensation were congestion (80.7%) and poor compliance/inadequate medication (43.4%), respectively. In the subanalysis of the 100 patients, systolic dysfunction was the most common cause of decompensation (55%); use of vasoactive drugs occurred in 20%, and mortality was 10%. The comparative analysis between the patients who were discharged and those who died during hospitalization confirmed some criteria of poor prognosis: reduced systolic blood pressure, low cardiac output associated with congestion, need for vasoactive drugs, reduced left ventricular ejection fraction, increased left ventricular diastolic diameter (LVDD) and hyponatremia. This study presents information about the profile of decompensated heart failure patients attended on the emergency unit of a brazilian southeast cardiology hospital. Clinical, hemodynamical and ancillary data may provide information for risk assessment in the initial evaluation helping the decision on hospitalization and advanced strategic therapies.