Investigating into microbiota in the uterine cavity of the unexplained recurrent pregnancy loss patients in early pregnancy.

INTRODUCTION: The majority of unexplained recurrent pregnancy loss (URPL) cases have been attributed to immune abnormalities. Inappropriate changes in microbiota could lead to immune disorders. However, the specific role of uterine cavity microbiota in URPL remains unclear, and only a limited number of related studies are available for reference. METHODS: We utilized double-lumen embryo transfer tubes to collect uterine cavity fluid samples from pregnant women in their first trimester. Subsequently, we conducted 16S rRNA sequencing to analyze the composition and abundance of the microbiota in these samples. RESULTS: For this study, we enlisted 10 cases of URPL and 28 cases of induced miscarriages during early pregnancy. Microbial communities were detected in all samples of the URPL group (100 %, n = 10), whereas none were found in the control group (0 %, n = 28). Among the identified microbes, Lactobacillus and Curvibacter were the two most dominant species. The abundance of Curvibacter is correlated with the number of NK cells in peripheral blood (r = -0.759, P = 0.018). DISCUSSION: This study revealed that during early pregnancy, Lactobacillus and Curvibacter were the predominant colonizers in the uterine cavity of URPL patients and were associated with URPL. Consequently, alterations in the dominant microbiota may lead to adverse pregnancy outcomes.

Real-World Outcomes of Everolimus and Exemestane for the Treatment of Metastatic Hormone Receptor-Positive Breast Cancer in Patients Previously Treated With CDK4/6 Inhibitors.

PURPOSE: Everolimus with exemestane (EVE+EXE) was FDA-approved to treat metastatic hormone receptor-positive breast cancer (mHRBC) based on BOLERO-2. However, none of those patients received prior CDK4/6 inhibitors. The purpose of this study is to evaluate the efficacy of EVE+EXE in mHRBC after CDK4/6 inhibitors. METHODS: A retrospective review of patients ≥18 years old with mHRBC treated with EVE+EXE, for ≥30 days, at our institution from January 1, 2012, to April 1, 2020 was conducted. Primary objective was to compare progression free survival (PFS) for EVE+EXE between patients with and without prior exposure to CDK4/6 inhibitors. Secondary outcomes included overall survival and safety. RESULTS: 192 patients were included in the study (n = 79, prior CDK4/6 inhibitor use; n = 113, no prior CDK4/6 inhibitor use). Baseline patient characteristics were similar between groups. Greater number of prior therapies before EVE+EXE use increased risk of disease progression (P = .017). Patients with prior CDK4/6 inhibitor use had a lower median PFS of 3.8 months (95% CI: 3.4-4.7) vs. 5.4 months (95% CI: 3.9-6.2) for patients without prior CDK4/6 inhibitor use, with a HR for progression of 1.46 (95% CI: 1.08 to 1.97, P = .013). Overall survival between groups was not significantly different. CONCLUSION: Patients who received a prior CDK4/6 inhibitor had a lower median PFS benefit from EVE+EXE compared to those who did not, without differences in overall survival. Although PFS is expected to decrease with subsequent lines of therapy, it is reasonable to use EVE+EXE after CDK4/6 inhibitors in selected patients, recognizing that additional benefit is modest.

A Review of Treatment-Induced Pulmonary Toxicity in Breast Cancer.

This article reviews the available literature that describes the incidence, diagnosis, mechanism, symptoms, and management of pulmonary toxicity induced by radiation therapy and current systemic medications used to treat breast cancer. An extensive literature search was conducted via Ovid Medline to identify all potentially relevant articles written in English from 2010 through January 2020. Additional relevant articles outside the time frame were included as needed. Although the risk of pulmonary toxicity from various breast cancer treatments is small in most instances, it can be fatal. Due to the high prevalence of breast cancer and the range of treatment options, healthcare providers should be aware of the risk of pulmonary toxicity from those treatments and how to prevent or manage complications.

Long Noncoding RNA RP11-115N4.1 Promotes Inflammatory Responses by Interacting With HNRNPH3 and Enhancing the Transcription of HSP70 in Unexplained Recurrent Spontaneous Abortion.

Background: Unexplained recurrent spontaneous abortion (URSA) is a common pregnancy complication and the etiology is unknown. URSA-associated lncRNAs are expected to be potential biomarkers for diagnosis, and might be related to the disease pathogenesis. Objective: To investigate differential lncRNAs in peripheral blood of non-pregnant URSA patients and matched healthy control women and to explore the possible mechanism of differential lncRNAs leading to URSA. Methods: We profiled lncRNAs expression in peripheral blood from 5 non-pregnant URSA patients and 5 matched healthy control women by lncRNA microarray analysis. Functions of URSA-associated lncRNAs were further investigated in vitro. Results: RP11-115N4.1 was identified as the most differentially expressed lncRNA which was highly upregulated in peripheral blood of non-pregnant URSA patients (P = 3.63E-07, Fold change = 2.96), and this dysregulation was further validated in approximately 26.67% additional patients (4/15). RP11-115N4.1 expression was detected in both lymphocytes and monocytes of human peripheral blood, and in vitro overexpression of RP11-115N4.1 decreased cell proliferation in K562 cells significantly. Furthermore, heat-shock HSP70 genes (HSPA1A and HSPA1B) were found to be significantly upregulated upon RP11-115N4.1 overexpression by transcriptome analysis (HSPA1A (P = 4.39E-08, Fold change = 4.17), HSPA1B (P = 2.26E-06, Fold change = 2.99)). RNA pull down and RNA immunoprecipitation assay (RIP) analysis demonstrated that RP11-115N4.1 bound to HNRNPH3 protein directly, which in turn activate heat-shock proteins (HSP70) analyzed by protein-protein interaction and HNRNPH3 knockdown assays. Most importantly, the high expression of HSP70 was also verified in the serum of URSA patients and the supernatant of K562 cells with RP11-115N4.1 activation, and HSP70 in supernatant can exacerbate inflammatory responses in monocytes by inducing IL-6, IL-1ß, and TNF-α and inhibit the migration of trophoblast cells, which might associate with URSA. Conclusion: Our results demonstrated that the activation of RP11-115N4.1 can significantly increase the protein level of HSP70 via binding to HNRNPH3, which may modulate the immune responses and related to URSA. Moreover, RP11-115N4.1 may be a novel etiological biomarker and a new therapeutic target for URSA.

Atosiban Combined with Ritodrine for Late Threatened Abortion or Threatened Premature Labor Patients with No Response to Ritodrine: A Clinical Trial.

BACKGROUND Premature labor is an important cause of infant death and long-term disability. This study aimed to explore the safety and effectiveness of combining the tocolytic agents atosiban and ritodrine to extend gestation. MATERIAL AND METHODS The study included 52 patients with late threatened abortion and threatened premature labor between 20°â¸7 and 336⸍7 weeks' gestation who were administrated continuous tocolytic agents for 48 h. Patients were divided into a research group receiving ritodrine combined with atosiban, owing to having no response to ritodrine alone (n=30), and a control group receiving ritodrine alone (n=22). The mean infusion rate and duration of tocolytic administration, gestation extension, pregnancy outcomes, and adverse effects were recorded. Routine blood tests, including C-reactive protein, and cultures for leukorrhea, candida, and mycoplasma were performed before and 1 week after treatment. RESULTS Patients receiving ritodrine with atosiban had a mean gestation extension of 42.53±31.70 days. The extension of gestation of the research group was statistically shorter than that of the control group (P<0.05). The fetal loss rate, newborn birth weight, and Apgar score at 1 min were similar between the 2 groups (all, P>0.05). The research group had a lower incidence of palpitations than the control group (P<0.05). CONCLUSIONS For patients with late threatened abortion or threatened premature labor not controlled with ritodrine alone, ritodrine combined with atosiban extends gestation and improves pregnancy outcomes. For patients with abnormal uterine contractions, routine testing for reproductive tract infection should be performed. When infection is present, anti-infective therapy should be administered.

Ketamine Safety and Use in the Emergency Department for Pain and Agitation/Delirium: A Health System Experience.

INTRODUCTION: Two protocols were developed to guide the use of subdissociative dose ketamine (SDDK) for analgesia and dissociative sedation ketamine for severe agitation/excited delirium in the emergency department (ED). We sought to evaluate the safety of these protocols implemented in 18 EDs within a large health system. METHODS: We conducted a retrospective chart review to evaluate all adult patients who received intravenous (IV) SDDK for analgesia and intramuscular (IM) dissociative sedation ketamine for severe agitation/excited delirium in 12 hospital-based and six freestanding EDs over a one-year period from the protocol implementation. We developed a standardized data collection form and used it to record patient information regarding ketamine use, concomitant medication use, and any comorbidities that could have impacted the incidence of adverse events. RESULTS: Approximately 570,000 ED visits occurred during the study period. SDDK was used in 210 ED encounters, while dissociative sedation ketamine for severe agitation/excited delirium was used in 37 ED encounters. SDDK was used in 83% (15/18) of sites while dissociative sedation ketamine was used in 50% (9/18) of sites. Endotracheal intubation, non-rebreather mask, and nasal cannula ≥ four liters per minute were identified in one, five, and three patients, respectively. Neuropsychiatric adverse events were identified in 4% (9/210) of patients who received SDDK. CONCLUSION: Patients experienced limited neuropsychiatric adverse events from SDDK. Additionally, dissociative sedation ketamine for severe agitation/excited delirium led to less endotracheal intubation than reported in the prehospital literature. The favorable safety profile of ketamine use in the ED may prompt further increases in usage.

Influence of Audiovisual Training on Horizontal Sound Localization and Its Related ERP Response.

The objective was to investigate the influence of audiovisual training on horizontal sound localization and the underlying neurological mechanisms using a combination of psychoacoustic and electrophysiological (i.e., event-related potential, ERP) measurements on sound localization. Audiovisual stimuli were used in the training group, whilst the control group was trained using auditory stimuli only. Training sessions were undertaken once per day for three consecutive days. Sound localization accuracy was evaluated daily after training, using psychoacoustic tests. ERP responses were measured on the first and last day of tasks. Sound localization was significantly improved in the audiovisual training group when compared to the control group. Moreover, a significantly greater reduction in front-back confusion ratio for both trained and untrained angles was found between pre- and post-test in the audiovisual training group. ERP measurement showed a decrease in N1 amplitude and an increase in P2 amplitude in both groups. However, changes in late components were only found in the audiovisual training group, with an increase in P400 amplitude and decrease in N500 amplitude. These results suggest that the interactive effect of audiovisual localization training is likely to be mediated at a relatively late cognitive processing stage.

[4 + 2] Annulation of 3-Nitroindoles with Alkylidene Malononitriles: Entry to Substituted Carbazol-4-amine Derivatives.

A general and transition-metal-free method for the construction of the carbazol-4-amine motif via a vinylogous Michael addition/cyclization/isomerization/elimination reaction of 3-nitroindoles with alkylidene malononitriles has been developed. This novel methodology allows the facile synthesis of a series of di- and trisubstituted carbazol-4-amine derivatives in moderate to good yields. A gram-scale experiment was successfully performed, highlighting the practicability of this method. Moreover, this strategy is also applicable to 3-nitrobenzothiophene, affording the corresponding dibenzo[ b, d]thiophen-1-amine derivatives in moderate yields.

Initial study of clinical pharmacy work prioritization tools.

PURPOSE: The development, implementation, and validity of clinical pharmacy work prioritization tools (CPWPTs) were analyzed. METHODS: Informatics pharmacists were contacted and asked to participate in 30-minute teleconference interviews, as they have primary responsibility for the technical configuration of CPWPTs. A total of 19 respondents participated in the survey. The qualitative data collected encompassed the thoughts and ideas of practicing informatics pharmacists who are knowledgeable about the design, configuration, management, and use of CPWPTs. In addition to capturing their thoughts and ideas with open-ended questions, demographic data were collected, as was information about the sites where respondents worked and the CPWPTs they used. RESULTS: Most of the CPWPTs were built into existing electronic health record platforms. There was considerable variation among the prioritization factors used at each site. The most commonly identified categories of prioritization factors were patient-specific factors, therapeutic classes of medications, and potential pharmacist interventions. All respondents reported that the prioritized tasks generated by their CPWPTs were examined for face validity. Of the 19 respondents, only 4 reported that the priorities generated by their CPWPT had been empirically validated in some way. Qualitative data analysis revealed that informatics pharmacists have 5 general perceptions about CPWPT factors, validation, and use in practice: (1) mirroring practice, (2) pharmacist consensus-based design, (3) complexity of logic, (4) tension between task-oriented and patient-centric approaches to practice, and (5) comfort from tracking tasks to completion. CONCLUSION: Early CPWPTs vary significantly in their prioritization factors. These tools partially reflect the scope of clinical pharmacy practice at the sites where they are used.

Vinylogous Elimination/Heck Coupling/Allylation Domino Reactions: Access to 2-Substituted 2,3-Dihydrobenzofurans and Indolines.

A highly regio- and stereoselctive palladium-catalyzed domino reaction of functionalized aryl allyl ethers has been developed. Various aryl allyl ethers derived from the phosphine-catalyzed addition of electron-deficient allenes with phenol are found to be efficient substrates for the synthesis of 2-substituted 2,3-dihydrobenzofurans and indolines. It is the first example of aryl allyl ether used as an ideal and practical precursor of hard to get functionalized 1,3-butadiene for the heterocyclic compound synthesis.

An elimination/Heck coupling/allylation cascade reaction: synthesis of 2,3-dihydrobenzofurans from allenoate adducts.

A highly regio- and stereoselective Pd-catalyzed cascade reaction of allenoate adducts has been developed. Various allenoate adducts of phosphine-catalyzed addition of allenoates are found to be efficient substrates for the preparation of 2,3-dihydrobenzofuran. It is the first example of allenoate adducts used as ideal and practical precursors of hard-to-get functionalized 1,3-butadienes for heterocycle synthesis.

Logistic regression analysis of factors influencing the effectiveness of intensive sound masking therapy in patients with tinnitus.

OBJECTIVES: To investigate factors influencing the effectiveness of intensive sound masking therapy on tinnitus using logistic regression analysis. DESIGN: The study used a retrospective cross-section analysis. PARTICIPANTS: 102 patients with tinnitus were recruited at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University, China. INTERVENTION: Intensive sound masking therapy was used as an intervention approach for patients with tinnitus. PRIMARY AND SECONDARY OUTCOME MEASURES: Participants underwent audiological investigations and tinnitus pitch and loudness matching measurements, followed by intensive sound masking therapy. The Tinnitus Handicap Inventory (THI) was used as the outcome measure pre and post treatment. Multivariate logistic regression was performed to investigate the association of demographic and audiological factors with effective therapy. RESULTS: According to the THI score changes pre and post sound masking intervention, 51 participants were categorised into an effective group, the remaining 51 participants were placed in a non-effective group. Those in the effective group were significantly younger than those in the non-effective group (P=0.012). Significantly more participants had flat audiogram configurations in the effective group (P=0.04). Multivariable logistic regression analysis showed that age (OR=0.96, 95% CI 0.93 to 0.99, P=0.007), audiometric configuration (P=0.027) and THI score pre treatment (OR=1.04, 95% CI 1.02 to 1.07, P<0.001) were significantly associated with therapeutic effectiveness. Further analysis showed that patients with flat audiometric configurations were 5.45 times more likely to respond to intervention than those with high-frequency steeply sloping audiograms (OR=5.45, 95% CI 1.67 to 17.86, P=0.005). CONCLUSION: Audiometric configuration, age and THI scores appear to be predictive of the effectiveness of sound masking treatment. Gender, tinnitus characteristics and hearing threshold measures do not seem to be related to treatment effectiveness. A further randomised control study is needed to provide evidence of the effectiveness of prognostic factors in tinnitus interventions.

Metal-free synthesis of allylic amines by cross-dehydrogenative-coupling of 1,3-diarylpropenes with anilines and amides under mild conditions.

Dehydrogenative cross-coupling reaction of primary anilines, secondary anilines, carboxamides, and sulfonamides with 1,3-diarylpropenes to form a series of allylic amines promoted by DDQ have been realized. Both monoallylation and diallylation products can be selectively synthesized when primary anilines are used as the starting materials. The method may provide a wide scope of allylamines in scientific research including biologically active compound library construction.

Iron-promoted synthesis of substituted 1-halo-1,4-pentadienes by reaction of 1,3-diarylpropenes with ethynylbenzenes via sp(3) C-H bond activation.

An iron-promoted sp(3) C-H bond activation and C-C bond formation reaction between 1,3-diarylpropenes and ethynylbenzenes was realized with BQ (benzoquinone) as an oxidant. The reaction afforded 1-halo-1,4-pentadiene derivatives in moderate to good yields under mild conditions.