A Systematic Review of Palpitations Prevalence by Menopausal Status

Purpose of the Review The purpose was to systematically review evidence on the prevalence of palpitations by menopausal stage. Palpitations are a feeling of missed, irregular, or exaggerated heart beats. Recent Findings Carefully delineated search, screening, and data extraction strategies resulted in five articles for review. Articles offered cross-sectional findings from menopausal symptom surveys from five countries between 1974 and 2011 with clinic- and community-based samples of premenopausal, perimenopausal, and postmenopausal women. Reported studies were good (n = 2) to fair (n = 3) quality with low (n = 2) to moderate (n = 3) bias. Menopausal palpitations were not the focus of any study but were assessed as a single item of heart racing, pounding, or discomfort over the past 2 weeks, month, or year. Palpitations prevalence rates by menopausal stage were 3.7 to 40.2% premenopausal, 20.1 to 40.2% perimenopausal, and 15.7 to 54.1% postmenopausal. Three of five articles showed that compared with premenopausal and postmenopausal women, palpitation prevalence was significantly higher among perimenopausal and surgically postmenopausal women. Summary Good-quality evidence on palpitation prevalence by menopausal stage is limited but suggests that physiological changes of menopause may play a role in this symptom. Measurement varied, suggesting a need to standardize the assessment of menopausal palpitations. The review findings suggest a strong need for clinicians and researchers to collaborate to standardize documentation of menopausal palpitations across the menopause transition

Field Research Is Essential to Counter Virological Threats

The interface between humans and wildlife is changing and, with it, the potential for pathogen introduction into humans has increased. Avian influenza is a prominent example, with an ongoing outbreak showing the unprecedented expansion of both geographic and host ranges. Research in the field is essential to understand this and other zoonotic threats. Only by monitoring dynamic viral populations and defining their biology in situ can we gather the information needed to ensure effective pandemic preparation.</p

Review of menopausal palpitations measures

Palpitations are reported commonly by women around the time of menopause as skipped, missed, irregular, and/or exaggerated heartbeats or heart pounding. However, much less is known about palpitations than other menopausal symptoms such as vasomotor symptoms. The objective of this review was to integrate evidence on menopausal palpitations measures. Keyword searching was done in PubMed, CINAHL, and PsycINFO for English-language, descriptive articles containing data on menopause and palpitations and meeting other pre-specified inclusion criteria. Of 670 articles, 110 met inclusion criteria and were included in the review. Results showed that 11 different measures were used across articles, with variability within and between measures. Inconsistencies in the wording of measurement items, recall periods, and response options were observed even when standardized measures were used. Most measures were limited to assessing symptom presence and severity. Findings suggest that efforts should be undertaken to (1) standardize conceptual and operational definitions of menopausal palpitations and (2) develop a patient-friendly, conceptually clear, psychometrically sound measure of menopausal palpitations

HCMV Targets the Metabolic Stress Response through Activation of AMPK Whose Activity Is Important for Viral Replication

Human Cytomegalovirus (HCMV) infection induces several metabolic activities that have been found to be important for viral replication. The cellular AMP-activated protein kinase (AMPK) is a metabolic stress response kinase that regulates both energy-producing catabolic processes and energy-consuming anabolic processes. Here we explore the role AMPK plays in generating an environment conducive to HCMV replication. We find that HCMV infection induces AMPK activity, resulting in the phosphorylation and increased abundance of several targets downstream of activated AMPK. Pharmacological and RNA-based inhibition of AMPK blocked the glycolytic activation induced by HCMV-infection, but had little impact on the glycolytic pathway of uninfected cells. Furthermore, inhibition of AMPK severely attenuated HCMV replication suggesting that AMPK is an important cellular factor for HCMV replication. Inhibition of AMPK attenuated early and late gene expression as well as viral DNA synthesis, but had no detectable impact on immediate-early gene expression, suggesting that AMPK activity is important at the immediate early to early transition of viral gene expression. Lastly, we find that inhibition of the Ca2+-calmodulin-dependent kinase kinase (CaMKK), a kinase known to activate AMPK, blocks HCMV-mediated AMPK activation. The combined data suggest a model in which HCMV activates AMPK through CaMKK, and depends on their activation for high titer replication, likely through induction of a metabolic environment conducive to viral replication

Virology under the microscope—a call for rational discourse

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology

Characterization of Specific Protein-RNA Complexes Associated with the Coupling of Polyadenylation and Last-Intron Removal

Polyadenylation and splicing are highly coordinated on substrate RNAs capable of coupled polyadenylation and splicing. Individual elements of both splicing and polyadenylation signals are required for the in vitro coupling of the processing reactions. In order to understand more about the coupling mechanism, we examined specific protein-RNA complexes formed on RNA substrates, which undergo coupled splicing and polyadenylation. We hypothesized that formation of a coupling complex would be adversely affected by mutations of either splicing or polyadenylation elements known to be required for coupling. We defined three specific complexes (A(C)′, A(C), and B(C)) that form rapidly on a coupled splicing and polyadenylation substrate, well before the appearance of spliced and/or polyadenylated products. The A(C)′ complex is formed by 30 s after mixing, the A(C) complex is formed between 1 and 2 min after mixing, and the B(C) complex is formed by 2 to 3 min after mixing. A(C)′ is a precursor of A(C), and the A(C)′ and/or A(C) complex is a precursor of B(C). Of the three complexes, B(C) appears to be a true coupling complex in that its formation was consistently diminished by mutations or experimental conditions known to disrupt coupling. The characteristics of the A(C)′ complex suggest that it is analogous to the spliceosomal A complex, which forms on splicing-only substrates. Formation of the A(C)′ complex is dependent on the polypyrimidine tract. The transition from A(C)′ to A(C) appears to require an intact 3′-splice site. Formation of the B(C) complex requires both splicing elements and the polyadenylation signal. A unique polyadenylation-specific complex formed rapidly on substrates containing only the polyadenylation signal. This complex, like the A(C)′ complex, formed very transiently on the coupled splicing and polyadenylation substrate; we suggest that these two complexes coordinate, resulting in the B(C) complex. We also suggest a model in which the coupling mechanism may act as a dominant checkpoint in which aberrant definition of one exon overrides the normal processing at surrounding wild-type sites

Human Cytomegalovirus Major Immediate-Early Proteins and Simian Virus 40 Large T Antigen Can Inhibit Apoptosis through Activation of the Phosphatidylinositide 3′-OH Kinase Pathway and the Cellular Kinase Akt

The temperature-sensitive cell line ts13 is mutated in CCG1, the gene encoding TAF(II)250, the largest of the TATA-binding protein-associated factors (TAFs) in TFIID. At the nonpermissive temperature, the temperature-sensitive phenotypes are (i) transcription defects, (ii) cell cycle arrest in G(1), and (iii) apoptosis. We previously demonstrated that the human cytomegalovirus (HCMV) major immediate-early proteins (MIEPs) can rescue the transcription defects and inhibit apoptosis at the nonpermissive temperature. In the work presented, we show that activation of the cellular kinase Akt alone can inhibit apoptosis in ts13 cells grown at the nonpermissive temperature. More significantly, we show that the HCMV MIEPs can activate Akt, resulting in the inhibition of apoptosis. In parallel experiments, we found that simian virus 40 (SV40) large T antigen can mediate the same function. These experiments were done by transfecting the HCMV major immediate-early gene or a cDNA encoding T antigen into ts13 cells, and thus neither viral attachment to receptors, viral tegument proteins, nor any other viral protein is required for Akt activation. Akt is activated by the phosphatidylinositide 3′-OH (PI3) kinase pathway. Using a specific inhibitor of PI3 kinase, we show that the ability of the MIEPs and T antigen to activate Akt and inhibit apoptosis is eliminated, suggesting that the viral proteins utilize the PI3 kinase pathway for Akt activation. Transfection of plasmids which express the individual 86-kDa (IEP86; IE2(579aa)) and 72-kDa (IEP72; IE1(491aa)) MIEPs indicate that each MIEP could inhibit apoptosis via activation of the PI3 kinase pathway

Microscopic and diagrammatic representations of the assembly compartment and nucleus in an HCMV-infected cell.

<p>(A) Maximum projection live cell micrograph showing the AC (identified by Dsred-tagged pp28, red) with the enlarged, kidney-shaped nucleus (identified by GFP-tagged lamin A) wrapped around the AC. (B) A poor artist's diagrammatic representation of the AC located next to the enlarged, kidney-shaped nucleus. The AC is formed on a microtubule organizing center (MTOC) with microtubules (MT) radiating from it. The nested cylindrical makeup of the AC is indicated by colored circles; each cylindrical region is proposed to be made up of vesicles derived from specific secretory organelles. Virion tegument and structural proteins reside with these vesicles and are applied to nucleocapsids as they egress from the nucleus and traverse toward the center of the AC. The point of contact between the AC and the nucleus may be a continuum, suggested by the dashed line representing the nuclear membrane at this junction. This may allow nucleocapsids open access from the nucleus to the AC late in infection. The AC and the kidney-shaped nucleus are formed by virally commandeered functions of dynein. Dynein (Dn) is shown pulling the nucleus around the AC by a mechanism similar to mitotic nuclear envelope breakdown. Dynein loaded with cargo (Dc) is shown to represent the formation of the AC.</p