Kofoedjespersen8761
Ciguatera poisoning can occur following the consumption of fish contaminated with trace levels of ciguatoxins (CTXs). These trace levels represent an analytical challenge for confirmation by LC-MS due to matrix interferences and the high instrument sensitivity required. Sample preparation procedures are laborious and require extensive cleanup procedures to address these issues. The application of a selective isolation technique employing boronate affinity polymers was therefore investigated for the capture of vic-diol-containing Caribbean and Pacific CTXs from fish extracts. A dispersive SPE procedure was developed where nearly complete binding of CTXs in fish extracts occurred with boric acid gel in less than 1 h. Release of the bound CTXs resulted in >95% recovery of C-CTX1/2, C-CTX3/4, CTX1B, 54-deoxyCTX1B, and 52-epi-54-deoxyCTX1B from the extracts. This selective extraction tool has the potential to greatly simplify both analytical sample preparation and preparative extraction and isolation of CTXs for structure elucidation and production of standards.
The GSK3732394 multivalent protein was developed as a novel, long-acting, antiretroviral biologic treatment regimen with three independent, non-cross-resistant mechanisms for inhibiting HIV-1 entry.
A single-centre, Phase 1, double-blind, randomized, placebo-controlled study was conducted in healthy volunteers, using a 2-part adaptive study design in Part 1, participants were randomized to receive subcutaneous injection of GSK3732394 or placebo (31) as single ascending doses (10-mg starting dose); in Part 2, participants were intended to receive multiple ascending doses. Primary and secondary objectives included safety, pharmacokinetics (PK) and pharmacodynamics (PD; cluster of differentiation four receptor occupancy [CD4 RO]) of GSK3732394 in healthy adults; PK/PD results in healthy volunteers were used to project HIV-1 treatment success.
The most frequently reported adverse event was injection site reactions (ISRs; 8/18 [44%]). Most ISRs were mild (Grade 1-2;
= 7); one participant experienced a Grade 3 ISR (erythema ≥10cm). All ISRs were delayed in onset (after Day 10). GSK3732394 demonstrated linear PK across all cohorts. Clearance was faster than expected, and PK/PD results were lower than expected, with the maximum dose investigated (80mg) achieving mean trough CD4 RO of ∼25% on Day 7. The study was terminated as the PK/PD model linking PK and CD4 RO indicated that the maximum planned doses would not achieve the desired therapeutic profile.
This study demonstrated successful deployment of PK/PD dose relationships in the design and conduct of clinical trials by leveraging the findings toward predicting probability of success, resulting in appropriate early termination (ClinicalTrials.gov, NCT03984812).
This study demonstrated successful deployment of PK/PD dose relationships in the design and conduct of clinical trials by leveraging the findings toward predicting probability of success, resulting in appropriate early termination (ClinicalTrials.gov, NCT03984812).
Higher urate levels are associated with higher systolic blood pressure (SBP) in adults, and in pregnancy with lower offspring birthweight. Mendelian randomization (MR) analyses suggest a causal effect of higher urate on higher SBP and of higher maternal SBP on lower offspring birthweight. If urate causally reduces birthweight, it might confound the effect of SBP on birthweight. We therefore tested for a causal effect of maternal urate on offspring birthweight.
We tested the association between maternal urate levels and offspring birthweight using multivariable linear regression in the Exeter Family Study of Childhood Health (EFSOCH; n = 872) and UK Biobank (UKB; n = 133 187). We conducted two-sample MR to test for a causal effect of maternal urate [114 single-nucleotide polymorphisms (SNPs); n = 288 649 European ancestry] on offspring birthweight (n = 406 063 European ancestry; maternal SNP effect estimates adjusted for fetal effects). We assessed a causal relationship between urate and SBP using one-samp of maternal urate on offspring birthweight compared with the multivariable regression result suggests previous observational associations may be confounded. The 95% CIs of the MR result included the null but suggest a possible small effect on birthweight. Maternal urate levels are unlikely to be an important contributor to offspring birthweight.
Depression and anxiety are highly prevalent among individuals struggling with infertility. Thus, numerous psychological interventions have been adapted to infertility, with the aim of relieving distress as well as increasing pregnancy rates.
This systematic review and meta-analysis aimed to identify all randomized controlled trials (RCTs) evaluating the effect of psychological interventions on infertility-related distress and pregnancy rates among individuals and/or couples with infertility and to analyse their overall effect. It also sought to examine potential treatment moderators, including intervention length, format and therapeutic approach.
An electronic search of 11 databases, including MEDLINE, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials, was performed for studies published until January 2022. The inclusion criteria were RCTs conducted on humans and published in English. Psychological outcomes of interest included anxiety, depression, infertility-related distress, wellbeis are associated with small reductions in distress and modest effects on conception, suggesting the need for more effective interventions. These findings must be considered in light of the fact that the majority of the included RCTs were deemed to be at high risk of bias. Rigorously conducted trials are needed.Cryopreserved ram spermatozoa are limited in their capacity to traverse the ovine cervix and achieve fertilisation. AZD3965 inhibitor This altered interaction may be related to modified molecular communication between frozen-thawed ram spermatozoa, seminal plasma and the female tract. As such, this review aims to identify the biological processes which underpin sperm maturation and transport throughout the female reproductive tract to elucidate factors which may alter this natural process in cryopreserved ram spermatozoa. We also assess critical barriers to ram spermatozoa specific to the ovine cervix and the role of seminal plasma in mitigating these barriers. Transcriptomics is explored as a new approach to understand the sperm-cervix interaction. Recent studies have demonstrated that both spermatozoa and seminal plasma contain a complex profile of coding and non-coding RNAs. These molecular species have clear links with functional fertility, and mounting evidence suggests they may be altered by cryopreservation. Emerging in vitro cell culture models are also investigated as a "next step" in studying this interaction, utilising transcriptomics to identify subtle changes in female tract gene expression in response to spermatozoa. The application of such models is proposed as an exciting opportunity to investigate the unique challenges faced by cryopreserved spermatozoa traversing the ovine cervix prior to fertilisation.
Goals of care conversations (GoCCs) are essential discussions, for those with chronic diseases, to identify a health care surrogate, initiate and review advance directives, and refer for palliative care. Prognosis with pulmonary hypertension (PH) related to heart failure (HF) remains challenging due to variation in trajectory of disease progression. The Gagne Combined Comorbidity score, an electronic prognostication score (E-Gagne), can be used to identify patients with high (>10%) 1-year mortality.
Implementation of E-Gagne tool to identify HF patients with high 1-year mortality risk and trigger GoCCs.
Plan-Do-Study-Act cycles were used throughout nine-week pre- and postintervention in an outpatient setting. Descriptive statistics and Chi-square analysis were used to compare GoCCs pre and post intervention.
Using the E-Gagne tool, PH patients with high mortality risk were identified, within 1 week of their scheduled appointments. GoCCs education was provided to all stakeholders. Medical records were reviewed for four aspects of GoCCs presence and review of advanced directive, documented health care surrogates, and referral for palliative care.
Documentation of GoCCs was greater postintervention compared with preintervention (0%, n = 0/47 and 88%, n = 35/40 respectively, p < .001). Documentation of each of the four aspects of GoCCs was variable with the greatest improvement in documentation of health care surrogate and review of advance directives. There were no referrals for palliative care (0%, n = 0/47 and 0%, n = 0/40).
Implementation of the E-Gagne tool, an electronic prognostication tool, identified high-risk PH HF patients and was effective in increasing documentation of GoCCs.
Implementation of the E-Gagne tool, an electronic prognostication tool, identified high-risk PH HF patients and was effective in increasing documentation of GoCCs.
Diabetes-related complications contribute to a costly health burden in the United States. Telehealth (TH) is a tool that can increase access to care and offer ongoing support for chronic disease self-management.
A primary care practice in Texas needed a method to manage an influx of patients with uncontrolled diabetes and improve type 2 diabetes outcomes using nurse practitioner (NP) TH appointments.
Thirty patients meeting inclusion criteria participated in monthly TH check-ins and followed monthly for 3 months. Baseline and postintervention diabetes laboratory studies (hemoglobin A1c [HbA1c], estimated glomerular filtration rate, and microalbumin) were collected.
During each monthly TH visit, an NP-led diabetes TH QI protocol was implemented. The Telehealth Usability Questionnaire was administered to patients after the 3-month intervention.
The TH QI protocol resulted in an overall ∼1% reduction in HbA1c. Over 73% of participants experienced various reductions of HbA1c, of which 2.3% achieved a postintervention HbA1c <7%, indicating controlled diabetes. Kidney function indicated by eGFR improved by 7 ml/min/1.73 m2 in 83% of participating patients. At the end of the 3-month intervention, 84% of participants expressed overall satisfaction with TH appointments.
Interventions using TH to improve chronic disease may be useful in diabetes outcomes and self-management. Monthly TH visits can improve patient outcomes, reduce complications, and enhance the patient-provider relationship. Preventive self-care activities and long-term use of TH visits for self-management are implications for future studies.
Interventions using TH to improve chronic disease may be useful in diabetes outcomes and self-management. Monthly TH visits can improve patient outcomes, reduce complications, and enhance the patient-provider relationship. Preventive self-care activities and long-term use of TH visits for self-management are implications for future studies.
Anterior capsular contraction syndrome (ACCS) describes the progressive fibrotic phimosis of the anterior capsular bag that usually occurs a few months after cataract surgery. YAG laser anterior capsulotomy (YAGAC) is the most common treatment option due to the low-risk profile of this intervention.
In this series, we evaluated the outcomes of an advanced nurse practitioner (ANP) in conducting this laser intervention, comparing the results with those of ophthalmologists.
Our study represents a single-centre, retrospective, continuous case series of 108 eyes that underwent YAGAC due to ACCS between January 2017 and July 2020 at the Birmingham and Midland Eye Centre, the second largest tertiary referral centre in the United Kingdom.
The groups treated by ANPs and ophthalmologists were similar in respect to age, gender, and laterality of the laser procedure. Eyes treated by ophthalmologists had significantly more ocular comorbidities (p < .001), the most common of which was glaucoma. Although the complication rate was higher in the ophthalmologist group, it did not reach statistical significance.
