Osmotic stress induces formation of both liquid condensates and amyloids by a yeast prion domain.

Liquid protein condensates produced by phase separation are involved in the spatiotemporal control of cellular functions, while solid fibrous aggregates (amyloids) are associated with diseases and/or manifest as infectious or heritable elements (prions). Relationships between these assemblies are poorly understood. The Saccharomyces cerevisiae release factor Sup35 can produce both fluid liquid-like condensates (e. g. at acidic pH) and amyloids (typically cross-seeded by other prions). We observed acidification-independent formation of Sup35-based liquid condensates in response to hyperosmotic shock in the absence of other prions, both at increased and physiological expression levels . The Sup35 prion domain, Sup35N, is both necessary and sufficient for condensate formation, while the middle domain, Sup35M antagonizes this process. Formation of liquid condensates in response to osmotic stress is conserved within yeast evolution. Notably, condensates of Sup35N/NM protein originated from the distantly related yeast Ogataea methanolica can directly convert to amyloids in osmotically stressed S. cerevisiae cells, providing a unique opportunity for real-time monitoring of condensate-to-fibril transition in vivo by fluorescence microscopy. Thus, cellular fate of stress-induced condensates depends on protein properties and/or intracellular environment.

Analysis of the Discharge Termination Mechanism of a Nonaqueous Li-O2 Battery Based on a Digital Reconstruction Model.

The service life of the lithium-oxygen (Li-O2) battery is an essential factor in measuring the performance of the battery, and it is also imperative to clarify the reason for battery termination. In this work, the positive electrode of a nonaqueous Li-O2 battery was selected after cutoff under different discharge conditions, and the digital reconstruction model of the positive electrode was carried out by X-CT technology. The reconstructed positive electrode's structural characteristics, material transport characteristics, and electrical conductivity were analyzed. It is found that the positive electrode has an apparent expansion phenomenon after constant capacity cyclic charge and discharge, but this situation is not evident after deep discharge. After the constant capacity test is cut off, the product distribution range in the positive electrode is more comprehensive and the material transport efficiency is higher. However, after deep discharge, the product distribution in the positive electrode is more concentrated and the material transport efficiency is lower. There are apparent differences in the termination mechanism between constant capacity cycle discharge and deep discharge. This paper provides a compelling theoretical basis for revealing the discharge termination mechanism of nonaqueous Li-O2 batteries.

Spontaneous termination of ventricular tachycardia in the human heart.

INTRODUCTION: Understanding the spatiotemporal location of the spontaneous termination of ventricular tachycardia (VT) may provide new insights for ablation. To test the hypothesis that spontaneous VT termination most frequently occurs at the VT exit due to source-sink mismatch and to characterize electrophysiological properties of the sites termination during VT and with extra-stimulus technique. METHODS: Retrospective analysis of intraoperative mapping studies of nine patients with ischemic cardiopathy or repaired tetralogy of Fallot. Simultaneous endocardial and epicardial mapping was performed in both ventricles using a custom mapping array during VT. Electrogram (EGM) characteristics before and at the moment of termination were analyzed including: cycle length oscillations, EGM heterogeneity and a variation in the systolic/diastolic path. The decrements to extra stimulus were analysed for termination sites and other diastolic sites. RESULTS: Nine VTs in seven patients demonstrated spontaneous VT termination. Seven VTs (77.8%) spontaneously terminated in the final third of the systolic interval, one (11.1%) in early diastole and one (11.1%) in mid diastole. Cycle length oscillations (prolongation, shortening, and no change) were seen in equal frequency. Four VTs (44.4%) showed alternans in the local EGM at the site of termination and this was more prevalent than alternans at other sites in the diastolic pathway (p < .001). Only one-third of VTs showed a change in activation pattern before termination. There was no difference based on etiology. During substrate characterization with extra-stimulus pacing, sites of spontaneous termination showed greater decrement than other sites of the VT circuit during pacing (43.5 ± 14.5 ms vs. 31.2 ± 31.2 ms; p = .003). CONCLUSION: The entrance zone rather than the exit is the commonest site for the spontaneous termination of VT in the human heart. These sites tend to demonstrate EGM alternans during VT and greater decrement during extrastimulus pacing. These findings may help guide future studies into improving the success of VT ablation.

Rli51 Attenuates Transcription of the Listeria Pathogenicity Island 1 Gene mpl and Functions as a Trans-Acting sRNA in Intracellular Bacteria.

Listeria pathogenicity island 1 (LIPI-1) is a genetic region containing a cluster of genes essential for virulence of the bacterial pathogen Listeria monocytogenes. Main virulence factors in LIPI-1 include long 5' untranslated regions (5'UTRs), among which is Rli51, a small RNA (sRNA) in the 5'UTR of the Zn-metalloprotease-coding mpl. So far, Rli51 function and molecular mechanisms have remained obscure. Here, we show that Rli51 exhibits a dual mechanism of regulation, functioning as a cis- and as a trans-acting sRNA. Under nutrient-rich conditions, rli51-mpl transcription is prematurely terminated, releasing a short 121-nucleotide-long sRNA. Rli51 is predicted to function as a transcription attenuator that can fold into either a terminator or a thermodynamically more stable antiterminator. We show that the sRNA Rli21/RliI binds to a single-stranded RNA loop in Rli51, which is essential to mediate premature transcription termination, suggesting that sRNA binding could stabilize the terminator fold. During intracellular infection, rli51 transcription is increased, which generates a higher abundance of the short Rli51 sRNA and allows for transcriptional read-through into mpl. Comparative intracellular bacterial transcriptomics in rli51-null mutants and the wild-type reference strain EGD-e suggests that Rli51 upregulates iron-scavenging proteins and downregulates virulence factors from LIPI-1. MS2 affinity purification confirmed that Rli51 binds transcripts of the heme-binding protein Lmo2186 and Lmo0937 in vivo. These results prove that Rli51 functions as a trans-acting sRNA in intracellular bacteria. Our research shows a growth condition-dependent mechanism of regulation for Rli51, preventing unintended mpl transcription in extracellular bacteria and regulating genes important for virulence in intracellular bacteria.

Risk Factors for Failure of Second-Trimester Termination with Misoprostol as a Single Agent.

Background: Understanding the potential risk factors for failure of pregnancy termination is crucial for informed clinical decision making. Such insights can assist clinicians in adjusting the dosage or route of various regimens, as well as in counseling patients and predicting the likelihood of successful outcomes. However, research on these risk factors has been limited, and existing studies have yielded inconsistent results. To address this gap, we conducted a study with a large sample size, focusing on identifying the potential risk factors for failure of second-trimester termination using misoprostol as a single agent, specifically between 14 and 28 weeks of gestation. Methods: A secondary analysis based on a database of second-trimester terminations was conducted. The inclusion criteria were a singleton pregnancy, gestational age between 14 and 28 weeks, an unfavorable cervix, no spontaneous labor pain, intact membranes, and termination with misoprostol alone. Potential risk factors for failure of termination, defined as no abortion within 48 h, were analyzed using univariate and multivariate analyses. Results: A total of 1094 cases were included in the analysis, consisting of 991 successful cases and 103 (9.4%) cases of failure. The significant risk factors for failure of termination included early gestational age, live fetuses, sublingual regimen of 400 mcg every 6 h, and high maternal pre-pregnancy BMI. Previous cesarean sections and lower Bishop scores tended to increase the risk but did not reach a significant level. Conclusions: Second-trimester termination with misoprostol as a single agent was highly effective, with a failure rate of 9.4%. The risk factors for failure included gestational age, fetal viability, misoprostol regimen, and maternal pre-pregnancy BMI, suggesting that these factors should be taken into consideration for second-trimester terminations with misoprostol.

Evaluation of levetiracetam loading dose in adult patients with benzodiazepine-refractory status epilepticus.

BACKGROUND: Status epilepticus (SE) is a neurologic emergency defined as continued seizure activity greater than five minutes or recurrent seizure activity without return to baseline. Benzodiazepine-refractory SE is continuous seizure activity despite treatment with a benzodiazepine. Treatment of benzodiazepine-refractory SE includes levetiracetam with loading doses ranging from 20 mg/kg to 60 mg/kg up to a maximum dose of 4500 mg. While levetiracetam has minimal adverse effects, there is currently a lack of studies directly comparing the safety and efficacy of various loading doses of levetiracetam. OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of three loading doses of levetiracetam in the setting of benzodiazepine-refractory SE. METHODS: This was a single center, retrospective cohort study of adult patients with benzodiazepine-refractory SE who were treated with levetiracetam from April 1, 2016, to August 31, 2023. Patients with documented hypersensitivity to levetiracetam, those who were pregnant or incarcerated and patients who received an alternative antiepileptic drug (AED) prior to levetiracetam were excluded. Patients with other identifiable causes of SE including hyperglycemia, hypoglycemia, hyponatremia or who were post cardiac arrest were also excluded. Patients were divided into three arms based on loading dose of levetiracetam administered (≤20 mg/kg [LEVlow], 21--39 mg/kg [LEVmed] or ≥40 mg/kg [LEVhigh]). The primary endpoint was the rate of seizure termination, defined as the lack of need for an additional AED within 60 min following levetiracetam administration. Secondary outcomes included the rate of intubation, and recurrent seizure activity 60 min to 24 h post seizure termination as defined by positive EEG results or need for an additional AED. Subgroup analyses were performed to assess the influence of adequate loading doses of benzodiazepines, and outpatient levetiracetam use. RESULTS: Overall, 740 patients were screened for inclusion, with 218 patients being included in the primary analysis. Patients were divided into three groups with an average levetiracetam loading dose of 14.5 mg/kg in the LEVlow group, 28.8 mg/kg in the LEVmed group, and 48.8 mg/kg in the LEVhigh group. There was no difference in rates of seizure termination at 60 min (92.9% LEVlow vs 89.3% LEVmed vs 84.7% LEVhigh; p = 0.377). Additionally, no difference was found in rates of recurrent seizure activity between 60 min and 24 h post levetiracetam loading dose (32.1% LEVlow vs 32.0% LEVmed vs 28.8% LEVhigh; p = 0.899). However, the LEVhigh group did have a higher rate of intubation (45.8%) compared to the LEVmed (28.2%) and LEVlow (26.8%) group (p = 0.040). CONCLUSION: The loading of levetiracetam did not result in a statistically significant difference in rate of seizure termination at 60 min nor did it appear to impact the rate of recurrent seizures at 24 h. However, we did find higher rates of intubation in patients who received levetiracetam >40 mg/kg. Further research is warranted to determine the optimal loading dose of levetiracetam in benzodiazepine-refractory SE.

Nonsense-Mediated mRNA Decay in Human Health and Diseases: Current Understanding, Regulatory Mechanisms and Future Perspectives.

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that is conserved across all eukaryotes ensuring the quality of transcripts by targeting messenger RNA (mRNA) harbouring premature stop codons. It regulates the gene expression by targeting aberrant mRNA carrying pre-termination codons (PTCs) and eliminates C-terminal truncated proteins. NMD distinguishes aberrant and non-aberrant transcript by looking after long 3' UTRs and exon-junction complex (EJC) downstream of stop codon that indicate the presence of PTC. Therefore, NMD modulates cellular surveillance and eliminates the truncated proteins but if the PTC escapes the surveillance pathway it can lead to potential negative phenotype resulting in genetic diseases. The alternative splicing also contributes in formation of NMD-sensitive isoforms by introducing PTC. NMD plays a complex role in cancer, it can either aggravate or downregulates the tumour. Some tumours agitate NMD to deteriorate mRNAs encoding tumour suppressor proteins, stress response proteins and neoantigens. In other case, tumours suppress the NMD to encourage the expression of oncoproteins for tumour growth and survival. This mechanism augmented in the development of new therapeutics by PTC read-through mechanism and personalized medicine. Detailed studies on NMD surveillance will possibly lead towards development of strategies for improving human health aligning with United Nations sustainable development goals (SDG 3: Good health and well-being). The potential therapeutic applications of NMD pose a challenge in terms of safe and effective modulation. Understanding the complexities of NMD regulation and its interaction with other cellular processes can lead to the development of new interventions for various diseases.

Molecular regulation of axon termination in mechanosensory neurons.

Spatially and temporally accurate termination of axon outgrowth, a process called axon termination, is required for efficient, precise nervous system construction and wiring. The mechanosensory neurons that sense low-threshold mechanical stimulation or gentle touch have proven exceptionally valuable for studying axon termination over the past 40 years. In this Review, we discuss progress made in deciphering the molecular and genetic mechanisms that govern axon termination in touch receptor neurons. Findings across model organisms, including Caenorhabditis elegans, Drosophila, zebrafish and mice, have revealed that complex signaling is required for termination with conserved principles and players beginning to surface. A key emerging theme is that axon termination is mediated by complex signaling networks that include ubiquitin ligase signaling hubs, kinase cascades, transcription factors, guidance/adhesion receptors and growth factors. Here, we begin a discussion about how these signaling networks could represent termination codes that trigger cessation of axon outgrowth in different species and types of mechanosensory neurons.

Repeat ablation of atrial fibrillation using electrogram dispersion to identify additional areas of mechanistic significance.

Background: Electrogram dispersion identifies putative atrial fibrillation (AF) drivers in first time ablation procedures, with high acute termination rates and long-term outcomes akin to extensive ablation approaches. Its use in a population that had undergone repeat ablation is unknown, particularly where the pulmonary veins are already isolated. Objective: This purpose of this study was to assess electrogram dispersion mapping during repeat ablation procedures for persistent AF. Methods: One hundred sixty-seven patients from the United Kingdom and Denmark, all with persistent AF recurrence after prior ablation procedure(s), were mapped using a five splined catheter for electrogram dispersion before ablation. Areas were manually tagged on biatrial electroanatomic maps and ablated once pulmonary vein isolation was confirmed or reisolated if required. All patients had 12-month continuous monitoring, with most of the cohort having follow-up beyond 24 months. Results: Of the 167 patients [53 (32%) female; mean age 66 ± 8 years; mean left atrial (LA) diameter 4.8 cm; mean ejection fraction 53%], 108 had pulmonary veins already isolated. Dispersion sites occurred in both atria (3.2 LA, 1.4 right atrium). Acute termination to sinus rhythm occurred in 71 (42%) of the cohort patients, with a further 73 (44%) terminating to atrial tachycardia/flutter. At 12-month follow-up, 95% of patients were free of AF, with 74% overall freedom from all atrial arrhythmias. Heart failure and severely enlarged LA predicted recurrence, and termination to sinus improved freedom from all atrial arrhythmias. Conclusion: Dispersion mapping is a promising approach at repeat ablation procedures for persistent AF, with high acute termination rates and good clinical outcomes. Further prospective randomized trials are needed to evaluate this approach in a population that had undergone repeat ablation.

Pik3c3 Expression Profiling in the Mouse Kidney and Its Role in Proximal Tubule Cell Physiology.

The class 3 phosphatidylinositol 3-kinase (Pik3c3) plays critical roles in regulating autophagy, endocytosis, and nutrient sensing, but its expression profile in the kidney remains undefined. Recently, we validated a Pik3c3 antibody through immunofluorescence staining of kidney tissues from cell type-specific Pik3c3 knockout mice. Immunohistochemistry unveiled significant disparities in Pik3c3 expression levels across various kidney cell types. Notably, renal interstitial cells exhibit minimal Pik3c3 expression. Further, co-immunofluorescence staining, utilizing nephron segment- or cell type-specific markers, revealed nearly undetectable levels of Pik3c3 expression in glomerular mesangial cells and endothelial cells. Intriguingly, although podocytes exhibit the highest Pik3c3 expression levels among all kidney cell types, the renal proximal tubule cells (RPTCs) express the highest level of Pik3c3 among all renal tubules. RPTCs are known to express the highest level of the epidermal growth factor receptor (EGFR) in adult kidneys; however, the role of Pik3c3 in EGFR signaling within RPTCs remains unexplored. Therefore, we conducted additional cell culture studies. The results demonstrated that Pik3c3 inhibition significantly delayed EGF-stimulated EGFR degradation and the termination of EGFR signaling in RPTCs. Mechanistically, Pik3c3 inhibition surprisingly did not affect the initial endocytosis process but instead impeded the lysosomal degradation of EGFR. In summary, this study defines, for the first time, the expression profile of Pik3c3 in the mouse kidney and also highlights a pivotal role of Pik3c3 in the proximal tubule cells. These findings shed light on the intricate mechanisms underlying Pik3c3-mediated regulation of EGFR signaling, providing valuable insights into the role of Pik3c3 in renal cell physiology.

Comparison of initial adenosine dose conversion rate for supraventricular tachycardia in the emergency department.

OBJECTIVE: To evaluate the rate of supraventricular tachycardia (SVT) termination between 6 mg and 12 mg initial adenosine doses. METHODS: This multi-center, retrospective cohort study evaluated patients presenting to the emergency department (ED) from January 1, 2020 to June 30, 2022 in SVT and received adenosine. The primary objective of the study is to compare the rate of SVT termination between adenosine 6 mg and 12 mg as documented on a formal electrocardiogram. Secondary endpoints include termination of SVT with subsequent adenosine dose, time to ED disposition, adverse effects, and subgroup analyses of patients with a body mass index greater than or equal to 40 kg/m2 and a history of SVT. RESULTS: Of 213 patients included, a 6 mg initial adenosine dose was administered to 117 patients (54.9 %) and a 12 mg initial adenosine dose was administered to 96 patients (45.1 %). SVT termination following the initial dose of 6 mg or 12 mg was 56.4 % and 79.1 %, respectively (p < 0.001). Among the 46 patients who failed to terminate SVT with an initial 6 mg dose, 33 converted to sinus rhythm with a subsequent adenosine dose in comparison to 1 of the 7 patients receiving an initial dose of 12 mg (71.7 % vs 14.3 %, p = 0.007). Median time to ED disposition, either inpatient admission or discharge, was 209 and 161 min, respectively (p = 0.104). There was no statistical difference in either subgroup analyses. CONCLUSION: A higher rate of SVT termination was observed with an initial adenosine dose of 12 mg in the ED in comparison to the guideline recommended dose of 6 mg. There were no significant differences in adverse effects observed.

Patterns of fitness and gene expression epistasis generated by beneficial mutations in the rho and rpoB genes of Escherichia coli during high-temperature adaptation.

Epistasis is caused by genetic interactions among mutations that affect fitness. To characterize properties and potential mechanisms of epistasis, we engineered eight double mutants that combined mutations from the rho and rpoB genes of Escherichia coli. The two genes encode essential functions for transcription, and the mutations in each gene were chosen because they were beneficial for adaptation to thermal stress (42.2°C). The double mutants exhibited patterns of fitness epistasis that included diminishing-returns epistasis at 42.2°C, stronger diminishing-returns between mutations with larger beneficial effects, and both negative and positive (sign) epistasis across environments (20.0°C and 37.0°C). By assessing gene expression between single and double mutants, we detected hundreds of genes with gene expression epistasis. Previous work postulated that highly-connected hub genes in co-expression networks have low epistasis, but we found the opposite: hub genes had high epistasis values in both co-expression and protein-interaction networks. We hypothesized that elevated epistasis in hub genes reflected that they were enriched for targets of Rho termination, but that was not the case. Altogether, gene expression and co-expression analyses revealed that thermal adaptation occurred in modules, through modulation of ribonucleotide biosynthetic processes and ribosome assembly, the attenuation of expression in genes related to heat shock and stress responses, and with an overall trend toward restoring gene expression towards the unstressed state.

The provision of abortion in Australia: service delivery as a bioethical concern.

Despite significant progress in the legalization and decriminalization of abortion in Australia over the past decade or more recent research and government reports have made it clear that problems with the provision of services remain. This essay examines such issues and sets forth the view that such issues can and should be seen as (bio)ethical concerns. Whilst conscientious objection-the right to opt-out of provision on the basis of clear ethical reservations-is a legally and morally permissible stance that healthcare professionals can adopt, this does not mean those working in healthcare can simply elect not to be providers absent a clear ethical rationale. Furthermore, simple non-provision would seem to contravene the basic tenants of medical professionalism as well as the oft raised claims of the healthcare professions to put the needs of patients first. Recognizing that much of the progress that has been made over the past three decades can be attributed to the efforts of dedicated healthcare professionals who have dedicated their careers to meeting the profession's collective responsibilities in this area of women's health and reproductive healthcare, this paper frames the matter as a collective ethical lapse on the part of healthcare professionals, the healthcare professions and those involved in the management of healthcare institutions. Whilst also acknowledging that a range of complex factors have led to the present situation, that a variety of steps need to be taken to ensure the proper delivery of services that are comprehensive, and that there has been an absence of critical commentary and analysis of this topic by bioethicists, I conclude that there is a need to (re)assess the provision of abortion in Australia at all levels of service delivery and for the healthcare professions and healthcare professionals to take lead in doing so. That this ought to be done is clearly implied by the healthcare profession's longstanding commitment to prioritizing the needs of patient over their own interests.

Detecting and Dating Early Non-live Pregnancy Outcomes: Generation of a Novel Pregnancy Algorithm From Norwegian Linked Health Registries.

PURPOSE: Pregnancies ending before gestational week 12 are common but not notified to the Medical Birth Registry of Norway. Our goal was to develop an algorithm that more completely detects and dates all possible pregnancy outcomes (i.e., miscarriages, elective terminations, ectopic pregnancies, molar pregnancies, stillbirths, and live births) by using diagnostic codes from primary and secondary care registries to complement information from the birth registry. METHODS: We used nationwide linked registry data between 2008 and 2018 in a hierarchical manner: We developed the UiO pregnancy algorithm to arrive at unique pregnancy outcomes, considering codes within 56 days as the same event. To estimate the gestational age of pregnancy outcomes identified in the primary and secondary care registries, we inferred the median gestational age of pregnancy markers (45 ICD-10 codes and 9 ICPC-2 codes) from pregnancies registered in the medical birth registry. When no pregnancy markers were available, we assigned outcome-specific gestational age estimates. The performance of the algorithm was assessed by blinded clinicians. RESULTS: Using only the medical birth registry, we identified 649 703 pregnancies, including 1369 (0.2%) miscarriages and 3058 (0.5%) elective terminations. With the new algorithm, we detected 859 449 pregnancies, including 642 712 live-births (74.8%), 112 257 miscarriages (13.1%), 94 664 elective terminations (11.0%), 6429 ectopic pregnancies (0.7%), 2564 stillbirths (0.3%), and 823 molar pregnancies (0.1%). The median gestational age was 10+1 weeks (IQR 10+0-12+2) for miscarriages and 8+0 weeks (IQR 8+0-9+6) for elective terminations. Gestational age could be inferred using pregnancy markers for 66.3% of miscarriages and 47.2% of elective terminations. CONCLUSION: The UiO pregnancy algorithm improved the detection and dating of early non-live pregnancy outcomes that would have gone unnoticed if relying solely on the medical birth registry information.

A quantitative model of temperature-dependent diapause progression.

Winter diapause in insects is commonly terminated through cold exposure, which, like vernalization in plants, prevents development before spring arrives. Currently, quantitative understanding of the temperature dependence of diapause termination is limited, likely because diapause phenotypes are generally cryptic to human eyes. We introduce a methodology to tackle this challenge. By consecutively moving butterfly pupae of the species Pieris napi from several different cold conditions to 20 °C, we show that diapause termination proceeds as a temperature-dependent rate process, with maximal rates at relatively cold temperatures and low rates at warm and extremely cold temperatures. Further, we show that the resulting thermal reaction norm can predict P. napi diapause termination timing under variable temperatures. Last, we show that once diapause is terminated in P. napi, subsequent development follows a typical thermal performance curve, with a maximal development rate at around 31 °C and a minimum at around 2 °C. The sequence of these thermally distinct processes (diapause termination and postdiapause development) facilitates synchronous spring eclosion in nature; cold microclimates where diapause progresses quickly do not promote fast postdiapause development, allowing individuals in warmer winter microclimates to catch up, and vice versa. The unveiling of diapause termination as one temperature-dependent rate process among others promotes a parsimonious, quantitative, and predictive model, wherein winter diapause functions both as an adaptation against premature development during fall and winter and for synchrony in spring.

TLN468 changes the pattern of tRNA used to read through premature termination codons in CFTR.

Nonsense mutations account for 12 % of cystic fibrosis (CF) cases. The presence of a premature termination codon (PTC) leads to gene inactivation, which can be countered by the use of drugs stimulating PTC readthrough, restoring production of the full-length protein. We recently identified a new readthrough inducer, TLN468, more efficient than gentamicin. We measured the readthrough induced by these two drugs with different cystic fibrosis transmembrane conductance regulator (CFTR) PTCs. We then determined the amino acids inserted at the S1196X, G542X, W846X and E1417X PTCs of CFTR during readthrough induced by gentamicin or TLN468. TLN468 significantly promoted the incorporation of one specific amino acid, whereas gentamicin did not greatly modify the proportions of the various amino acids incorporated relative to basal conditions. The function of the engineered missense CFTR channels corresponding to these four PTCs was assessed with and without potentiator. For the recoded CFTR, except for E1417Q and G542W, the PTC readthrough induced by TLN468 allowed the expression of CFTR variants that were correctly processed and had significant activity that was enhanced by CFTR modulators. These results suggest that it would be relevant to assess the therapeutic benefit of TLN468 PTC suppression in combination with CFTR modulators in preclinical assays.

Periviability for the Ob-Gyn Hospitalist.

Periviable birth refers to births occurring between 20 0/7 and 25 6/7 weeks gestational age. Management of pregnant people and neonates during this fragile time depends on the clinical status, as well as the patient's wishes. Providers should be prepared to counsel patients at the cusp of viability, being mindful of the uncertainty of outcomes for these neonates. While it is important to incorporate the data on projected morbidity and mortality into one's counseling, shared-decision making is most essential to caring for these patients and optimizing outcomes for all.

Outcomes and complications of second-trimester induction of labor using laminaria and gemeprost: A single-center experience in Japan.

AIM: To document the outcomes of second-trimester induction of labor with laminaria cervical dilation followed by gemeprost vaginal tablets, with a particular emphasis on its complications. METHODS: This was a single-center retrospective cohort study of women who experienced medical abortions between 12 and 21 weeks of gestation from January 2016 to July 2021. Procedures were performed with three laminaria cervical dilation for 2 days followed by the administration of gemeprost (1 mg, vaginal tablet) every 3 h with a maximum of five tablets per day. Epidural anesthesia was provided upon request. The primary outcome was successful labor induction, which was defined as fetal expulsion without assisted surgical procedures. Other maternal outcomes, complications and related interventions during and after the procedure were assessed. RESULTS: Among 319 women, 313 (98.1%) experienced successful labor induction with a median of one gemeprost tablet. The median blood loss during the abortion was 145 mL, and three women (0.9%) required blood transfusion. Fever was observed in 19 women (6.0%) during hospitalization, although most cases were drug fever. Thirteen women (4.1%) had abnormal uterine bleeding ~24 days after the abortion. Eleven cases (3.4%) were associated with retained products of conception, of which three cases required uterine artery embolization and three needed surgical curettage. CONCLUSIONS: Second-trimester induction of labor with laminaria cervical dilation and subsequent gemeprost vaginal tablets is a reliable method for completing medical abortions. Abnormal uterine bleeding several weeks after abortion is suspected to be a retained product of conception that could require invasive treatment.

Trends, spatiotemporal variation and decomposition analysis of pregnancy termination among women of reproductive age in Ethiopia: Evidence from the Ethiopian demographic and health survey, from 2000 to 2016.

Background: Pregnancy termination is a major public health problem, and complications of unsafe abortion are among the proximate and major causes of maternal mortality. Mapping the trend and spatiotemporal variation and identifying factors that are responsible for the changes in pregnancy termination help achieve the sustainable development goal of reducing maternal mortality in Ethiopia by understanding the epidemiology and regional variations. Methods: Data from the 2000-2016 Ethiopian Demographic and Health Survey were analyzed with a total weighted sample of 40,983 women of reproductive age. Variables with a p-value <0.05 in a logit multivariable decomposition analysis were considered significant predictors of the decline in pregnancy termination over time. Spatial analysis was used separately for each survey to show the changes in regional disparities in pregnancy termination in Ethiopia. Results: The magnitude of pregnancy termination among women of reproductive age decreased by 39.5 %, from 17.7 % in 2000 to 10.7 % in 2016. The difference in the effects of literacy, working status, marital status, age at first intercourse, age at first cohabitation, knowledge about contraceptives, and knowledge of the ovulatory cycle were the significant predictors that contributed to the change in pregnancy termination over time. Significant clusters of pregnancy terminations were observed in central and northern Ethiopia (Addis Ababa, eastern Amhara, and Tigray regions). Conclusions: Despite the substantial decrease in terminated pregnancies over time in Ethiopia, the magnitude is still high. The government should focus on promoting education for girls and women, providing reproductive health education, including access to contraceptives, and raising the minimum age for girls to engage in sexual activities or marriage by implementing policies.

The Effect of Heat Aging on the Microstructure and Properties of Spray-Deposited AlZnMgCu Alloy Extruded Plates.

The heat-aging process, a practical aging technology that not only improves the comprehensive performance of Al alloys but also reflects the requirements of short processes, has an extremely practical significance. The effects of the heating rate and termination temperature on the "heat-aging" behavior of a spray-deposited AlZnMgCu alloy hot-extruded plate were investigated using hardness, electrical conductivity, room-temperature tensile strength, exfoliation corrosion experiments, and transmission electron microscopy microstructure (TEM) observation. The results show that as the termination temperature increases, the hardness of the spray-deposited AlZnMgCu alloy first increases to a peak and then rapidly decreases, while the electrical conductivity continues to increase. The increase in the heating rate improves the peak hardness corresponding to the termination temperature. The heat treatment process of heating at a speed of 20 °C/h to 200 °C after the spray deposition has similar mechanical and corrosion resistance properties to the RRA process and can effectively reduce the heating time from 40 h to 8 h, thus establishing a heat treatment process for spray-deposited AlZnMgCu alloy extruded plate with high aging efficiency.