Bracketed Stability Evaluation of Methimazole USP in PLO Gel Mediflo™30 Pre-Mixed.

Extemporaneously compounded Methimazole 1% and 10% in PLO Gel Mediflo™30 Pre-Mixed were studied to assess physical, chemical and microbial stability over time. The formulations were stored at room temperature in tightly closed, light resistant plastic containers. Chemical stability was evaluated using a validated, stability indicating HPLC analysis and physical stability was evaluated through observation of organoleptic appearance and pH measurement at predetermined time points. Lastly, antimicrobial effectiveness testing was conducted per USP <51> guidelines. The results indicate that compounded Methimazole remained within the stability criteria for the duration of the study and can be assigned an extended beyond-use-date of 120 days under the studied conditions.

Predictors of Invasive Bacterial Infection in Febrile Infants Aged 2 to 6 Months in the Emergency Department.

Our goal was to identify predictors of invasive bacterial infection (ie, bacteremia and bacterial meningitis) in febrile infants aged 2-6 months. In our multicenter retrospective cohort, older age and lower temperature identified infants at low risk for invasive bacterial infection who could safely avoid routine testing.

Exposure to microplastics and human reproductive outcomes: A systematic review.

BACKGROUND: Microplastics, produced through degradation of environmental plastic pollution, have been detected in human tissues including placenta and fetal meconium. Cell culture and animal studies have demonstrated potential reproductive toxicity of these particles; however, their association with adverse fertility or pregnancy outcomes in humans is not known. OBJECTIVES: To synthesise evidence for the presence of microplastics in human reproductive tissue and their associations with environmental exposures and reproductive outcomes. SEARCH STRATEGY: MEDLINE, Embase, Emcare, CINAHL, ClinicalTrials.gov and ICTRP were searched from inception to 03/02/2023. SELECTION CRITERIA: Studies of human participants, assessing presence of microplastics in reproductive tissues, environmental exposures to microplastics, and fertility- or pregnancy-related outcomes. DATA COLLECTION AND ANALYSIS: Two independent reviewers selected studies and extracted data on study characteristics, microplastics detected, environmental exposures and reproductive outcomes. Narrative synthesis was performed due to methodological heterogeneity. MAIN RESULTS: Of 1094 citations, seven studies were included, covering 96 participants. Microplastics composed of 16 different polymer types were detected in both placental and meconium samples. Two studies reported associations between lifestyle factors (daily water intake, use of scrub cleanser or toothpaste, bottled water and takeaway food) and placental microplastics. One study reported associations between meconium microplastics and reduced microbiota diversity. One reported placental microplastic levels correlated with reduced birthweights and 1-minute Apgar scores. CONCLUSIONS: There is a need for high-quality observational studies to assess the effects of microplastics on human reproductive health.

Impact of COVID-19 on gestational diabetes pregnancy outcomes in the UK: A multicentre retrospective cohort study.

OBJECTIVE: To determine the impact of implementing emergency care pathway(s) for screening, diagnosing and managing women with gestational diabetes (GDM) during COVID-19. DESIGN: Retrospective multicentre cohort. SETTING: Nine National Health Service (NHS) Hospital Trusts/Health boards in England and Scotland. POPULATION: 4915 women with GDM pre-pandemic (1 April 2018 to 31 March 2020), and 3467 women with GDM during the pandemic (1 May 2020 to 31 March 2021). METHODS: We examined clinical outcomes for women with GDM prior to and during the pandemic following changes in screening methods, diagnostic testing, glucose thresholds and introduction of virtual care for monitoring of antenatal glycaemia. MAIN OUTCOME MEASURES: Intervention at birth, perinatal mortality, large-for-gestational-age infants and neonatal unit admission. RESULTS: The new diagnostic criteria more often identified GDM women who were multiparous, had higher body mass index (BMI) and greater deprivation, and less frequently had previous GDM (all p < 0.05). During COVID, these women had no differences in the key outcome measures. Of the women, 3% were identified with pre-existing diabetes at antenatal booking. Where OGTT continued during COVID, but virtual care was introduced, outcomes were also similar pre- and during the pandemic. CONCLUSIONS: Using HbA1c and fasting glucose identified a higher risk GDM population during the pandemic but this had minimal impact on pregnancy outcomes. The high prevalence of undiagnosed pre-existing diabetes suggests that women with GDM risk factors should be offered HbA1c screening in early pregnancy.

Racial Differences in the Diagnosis of Lyme Disease in Children.

Black children with Lyme disease compared with children of other races were less likely to have an erythema migrans lesion diagnosed (adjusted odds ratio, 0.34; 95% confidence interval, .14-.79) but more likely to have a swollen joint (adjusted odds ratio, 3.68; 95% confidence interval, 2.13-6.36) after adjustment for age and local Lyme incidence.

Development of a clinical practice guideline for weaning and discontinuing parenteral nutrition in hospitalized children as part of a central line-associated bloodstream infection-focused quality improvement initiative.

BACKGROUND: Overprescribing of parenteral nutrition (PN) increases costs and risks to patients, including from central line-associated bloodstream infection (CLABSI). With CLABSI reduction in mind, our children's hospital began an iterative quality improvement effort to decrease PN utilization by first ensuring appropriate initiation and then defining and ensuring appropriate discontinuation. METHODS: Education was launched along with audits to evaluate for appropriate PN indications. Next, a literature review was conducted to guide the development of an algorithm to appropriately wean and discontinue PN. Lastly, all PN discontinuations were audited for agreement with the new guideline. Retrospectively, monthly PN utilization index (orders per patient-day) was plotted on a statistical process control chart to assess change over time. The presence of PN as a risk factor for CLABSI events and the overall hospital CLABSI rate were trended. RESULTS: Mean PN utilization index fell from 0.156 (July 2018 to January 2019) to 0.12 (February 2019 to August 2020) (P < .01). For 18 months, no PN utilization index reached the baseline lower control limit of 0.144, demonstrating special-cause variation and sustained change. PN as a risk factor for hospital CLABSI cases decreased from most prevalent (49% of cases) to fifth most prevalent (29%) as the CLABSI rate trended down. CONCLUSION: Engaging frontline staff in the development of a clinical practice guideline and increased accountability to reduce potential patient harm led to a significant and sustained reduction in PN utilization, as well as decreased prevalence of PN as a risk factor in hospital CLABSI cases.

Hospital admission as a deprescribing triage point for patients discharged to Residential Aged Care Facilities.

BACKGROUND: Deprescribing may benefit older frail patients experiencing polypharmacy. We investigated the scope for deprescribing in acutely hospitalised patients and the long-term implications of continuation of medications that could potentially be deprescribed. METHODS: Acutely hospitalised patients (n = 170) discharged to Residential Aged Care Facilities, ≥75 years and receiving ≥5 regular medications were assessed during admission to determine eligibility for deprescribing of key drug classes, along with the actual incidence of deprescribing. The impact of continuation of nominated drug classes (anticoagulants, antidiabetics, antiplatelets, antipsychotics, benzodiazepines, proton pump inhibitors (PPIs), statins) on a combined endpoint (death/readmission) was determined. RESULTS: Hyperpolypharmacy (>10 regular medications) was common (49.4%) at admission. Varying rates of deprescribing occurred during hospitalisation for the nominated drug classes (8-53%), with considerable potential for further deprescribing (34-90%). PPI use was prevalent (56%) and 89.5% of these had no clear indication. Of the drug classes studied, only continued PPI use at discharge was associated with increased mortality/readmission at 1 year (hazard ratio 1.54, 95% confidence interval (1.06-2.26), P = 0.025), driven largely by readmission. CONCLUSION: There is considerable scope for acute hospitalisation to act as a triage point for deprescribing in older patients. PPIs in particular appeared overprescribed in this susceptible patient group, and this was associated with earlier readmission. Polypharmacy in older hospitalised patients should be targeted for possible deprescribing during hospitalisation, especially PPIs.

Lithium Chloride Sensitivity in Yeast and Regulation of Translation.

For decades, lithium chloride (LiCl) has been used as a treatment option for those living with bipolar disorder (BD). As a result, many studies have been conducted to examine its mode of action, toxicity, and downstream cellular responses. We know that LiCl is able to affect cell signaling and signaling transduction pathways through protein kinase C and glycogen synthase kinase-3, which are considered to be important in regulating gene expression at the translational level. However, additional downstream effects require further investigation, especially in translation pathway. In yeast, LiCl treatment affects the expression, and thus the activity, of PGM2, a phosphoglucomutase involved in sugar metabolism. Inhibition of PGM2 leads to the accumulation of intermediate metabolites of galactose metabolism causing cell toxicity. However, it is not fully understood how LiCl affects gene expression in this matter. In this study, we identified three genes, NAM7, PUS2, and RPL27B, which increase yeast LiCl sensitivity when deleted. We further demonstrate that NAM7, PUS2, and RPL27B influence translation and exert their activity through the 5'-Untranslated region (5'-UTR) of PGM2 mRNA in yeast.

Taking stock: A systematic review of archaeological evidence of cancers in human and early hominin remains.

This study summarizes data from 154 paleopathological studies documenting 272 archaeologically recovered individuals exhibiting skeletal or soft tissue evidence of cancer (malignant neoplastic disease) between 1.8 million years ago and 1900 CE. The paper reviews and summarizes the temporal, spatial and demographic distribution of the evidence and the methods used to provide the cancer diagnoses. Metastasis to bone is the most widely reported evidence (n = 161), followed by multiple myeloma (n = 55). In the dataset, males were represented more than females (M = 127, F = 94), and middle-adults (35-49) and old-adults (50+) were represented most among age groups (MA = 77, OA = 66). The majority of the evidence comes from Northern Europe (n = 51) and Northern Africa (n = 46). The data are summarized in the Cancer Research in Ancient Bodies (CRAB) Database, a growing online resource for future paleo-oncological research. This systematic review contributes to broader studies of malignant neoplastic disease in antiquity; it provides an overview of paleo-oncological data, discusses the many practical and methodological challenges of paleo-oncological research, and dispels presumptions about cancer's rarity in the past.

Paleo-oncology: Taking stock and moving forward.

This article serves as an introduction to the International Journal of Paleopathology's special issue, Paleo-oncology: Taking Stock and Moving Forward. Reflecting the goals of the special issue, this paper has been designed to provide an overview of the current state of paleo-oncology, to introduce new and innovative paleo-oncological research and ideas, and to serve as a catalyst for future discussions and progress. This paper begins with an overview of the paleo-oncological evidence that can be found in ancient remains, followed by a summary of significant paleo-oncological findings and methodological advances to date. Thereafter, challenges in estimating past prevalence of cancer are highlighted and recommendations are made for future advancements in paleo-oncological research. The ground-breaking studies included in the special issue and referenced throughout this introduction embody the many ways in which progress can be made in the field of paleo-oncology.

Definitions and reporting of placental insufficiency in biomedical journals: a review of the literature.

Placental insufficiency is a major problem worldwide for both mothers and babies. However, we have demonstrated in a review of the biomedical literature, that both the terminology used to describe, and techniques used to measure suboptimal placental function, are remarkably varied and inconsistent in both clinical and scientific studies. We, therefore, present a case for the development of a standardised approach to studying placental insufficiency.

Syncytiotrophoblast Extracellular Vesicles from Pre-Eclampsia Placentas Differentially Affect Platelet Function.

Pre-eclampsia (PE) complicates around 3% of all pregnancies and is one of the most common causes of maternal mortality worldwide. The pathophysiology of PE remains unclear however its underlying cause originates from the placenta and manifests as raised blood pressure, proteinuria, vascular or systemic inflammation and hypercoagulation in the mother. Women who develop PE are also at significantly higher risk of subsequently developing cardiovascular (CV) disease. In PE, the failing endoplasmic reticulum, oxidative and inflammatory stressed syncytiotrophoblast layer of the placenta sheds increased numbers of syncytiotrophoblast extracellular vesicles (STBEV) into the maternal circulation. Platelet reactivity, size and concentration are also known to be altered in some women who develop PE, although the underlying reasons for this have not been determined. In this study we show that STBEV from disease free placenta isolated ex vivo by dual placental perfusion associate rapidly with platelets. We provide evidence that STBEV isolated from normal placentas cause platelet activation and that this is increased with STBEV from PE pregnancies. Furthermore, treatment of platelets with aspirin, currently prescribed for women at high risk of PE to reduce platelet aggregation, also inhibits STBEV-induced reversible aggregation of washed platelets. Increased platelet reactivity as a result of exposure to PE placenta derived STBEVs correlates with increased thrombotic risk associated with PE. These observations establish a possible direct link between the clotting disturbances of PE and dysfunction of the placenta, as well as the known increased risk of thromboembolism associated with this condition.

Merging of long-term memories in an insect.

Research on comparative cognition has largely focused on successes and failures of animals to solve certain cognitive tasks, but in humans, memory errors can be more complex than simple failures to retrieve information [1, 2]. The existence of various types of "false memories," in which individuals remember events that they have never actually encountered, are now well established in humans [3, 4]. We hypothesize that such systematic memory errors may be widespread in animals whose natural lifestyle involves the processing and recollection of memories for multiple stimuli [5]. We predict that memory traces for various stimuli may "merge," such that features acquired in distinct bouts of training are combined in an animal's mind, so that stimuli that have never been viewed before, but are a combination of the features presented in training, may be chosen during recall. We tested this using bumblebees, Bombus terrestris. When individuals were first trained to a solid single-colored stimulus followed by a black and white (b/w)-patterned stimulus, a subsequent preference for the last entrained stimulus was found in both short-term- and long-term-memory tests. However, when bees were first trained to b/w-patterned stimuli followed by solid single-colored stimuli and were tested in long-term-memory tests 1 or 3 days later, they only initially preferred the most recently rewarded stimulus, and then switched their preference to stimuli that combined features from the previous color and pattern stimuli. The observed merging of long-term memories is thus similar to the memory conjunction error found in humans [6].

False memory susceptibility is correlated with categorisation ability in humans.

Our memory is often surprisingly inaccurate, with errors ranging from misremembering minor details of events to generating illusory memories of entire episodes. The pervasiveness of such false memories generates a puzzle: in the face of selection pressure for accuracy of memory, how could such systematic failures have persisted over evolutionary time? It is possible that memory errors are an inevitable by-product of our adaptive memories and that semantic false memories are specifically connected to our ability to learn rules and concepts and to classify objects by category memberships. Here we test this possibility using a standard experimental false memory paradigm and inter-individual variation in verbal categorisation ability. Indeed it turns out that the error scores are significantly negatively correlated, with those individuals scoring fewer errors on the categorisation test being more susceptible to false memory intrusions in a free recall test. A similar trend, though not significant, was observed between individual categorisation ability and false memory susceptibility in a word recognition task. Our results therefore indicate that false memories, to some extent, might be a by-product of our ability to learn rules, categories and concepts.

The "Birmingham stitch"--avoiding slippage in laparoscopic gastric banding.

BACKGROUND: Slippage rates of 1.4-24 % are frequently quoted after adjustable gastric banding. This complication can be extremely serious and has contributed to many units offering more invasive interventions in the surgical management of morbid obesity. We present results of the first 1,140 Laparoscopic Bands performed in our unit. METHODS: Between April 2003 and June 2007, 1140 consecutive patients, mean weight 121.5 kg (range 73-268 kg), mean body mass index (BMI) 44.3 kg/m(2) (range 35-88) underwent laparoscopic adjustable gastric banding (LAGB). An identical surgical technique of one gastropexy suture in addition to the two routine gastro-gastro tunnel sutures was used in all cases. Fluoroscopy-guided adjustments were performed at 3 and 6 months and fluoroscopic evaluations were performed later if clinically indicated. RESULTS: There was no mortality and only one major septic complication of gastric perforation 1 week postoperatively which was managed conservatively. The mean stay was 1.02 days (range 0-30 days). Excess percent BMI loss in these patients at 3, 6, 12, 18, 24, 30, and 36 months were 25.4%, 34.7%, 38.3%, 41.1%, 43.7%, 44.4%, and 58.9%, respectively. Slippage with urgent readmission occurred in one patient (0.08%) at 5 months. Two partial slippages were noticed at 12 and 18 months, respectively. One patient had the band removed and the other was treated by band deflation and repositioning 6 months later. CONCLUSION: These results demonstrate that in our unit, laparoscopic gastric band insertion is successful in producing weight loss and at the same time has a very low slippage and pouch dilatation rate. This difference is most probably secondary to operative technique.

Obesity and hypertension among children after treatment for acute lymphoblastic leukemia.

BACKGROUND: The purpose was to determine the prevalence and treatment-related risk factors for obesity and hypertension among childhood acute lymphoblastic leukemia (ALL) survivors treated with contemporary therapy. METHODS: In a single-center longitudinal study, serial body mass indices (BMI) and blood pressure (BP) measurements of children ages 2-20 at time of ALL diagnosis and enrolled on pediatric cooperative group trials from 1993-2003 were abstracted from medical records and converted to population-referenced z-scores. RESULTS: Among 165 study participants, BMI z-scores increased significantly between diagnosis (median age 4.8 years) and therapy completion. At the end of therapy, 17.0% of survivors were overweight (BMI of 25-29, or 85-94% for age), 21.2% were obese (BMI >or=30, or >or=95% for age), and 15.3% had BP meeting stage 1+ hypertension thresholds (systolic or diastolic BP >or=140/90 mm Hg, or 95% for age and height plus 5 mm Hg). These proportions were found to be unchanged 2-3 years later. In multivariate analysis, the highest level of corticosteroid exposure was associated with both obesity (odds ratio [OR] 6.0; 95% confidence interval [95% CI], 1.2-28.5) as well as stage 1+ hypertension (OR 2.4; 95% CI, 1.2-5.1) compared with the lowest level. Females also were more likely to have increased BMI and elevated BP compared with males. Treatment intensity and cranial radiotherapy were not found to be associated with BMI or BP changes. CONCLUSIONS: Despite reductions in the use of cranial radiotherapy, contemporary childhood survivors of ALL remain at an increased risk of obesity and hypertension at least several years after the completion of treatment, with those exposed to higher doses of corticosteroids at greater risk.