Distinct Inflammatory Phenotypes are associated with subclinical and clinical Cardiovascular disease in People living with HIV.

Despite inflammation being implicated in cardiovascular disease (CVD) in people with HIV (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in two independent cohorts of PWH. We identified three distinct inflammatory clusters present in both cohorts that associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH.

HIV and fracture: Risk, assessment and intervention.

OBJECTIVES: With management of comorbidity in people living with HIV (PLWH) a key component of clinical care, early loss of bone integrity and clinical fracture are recognized as important issues. This review aims to describe the epidemiology of fracture in PLWH, as well as summarizing the relative balance of factors that contribute to fracture. We also aim to describe fracture risk assessment and interventional strategies to modify the risk of fracture in this population. RESULTS: Data from recent meta-analyses show that PLWH have significantly more fractures than the general population, with men and injecting drug users at higher risk. Modifiable factors that contribute to fracture risk in this cohort include body mass index (BMI), drug use, concurrent medications, frailty, and hepatitis C virus infection. Relating to antiretroviral therapy, current or ever tenofovir exposure has been identified as predictive of fracture but not cumulative use, and a potentially modest protective effect of efavirenz has been observed. Fracture Risk Assessment Tool scores underestimate fracture risk in PLWH with improved accuracy when HIV is considered a cause of secondary osteoporosis and bone mineral density (BMD) included. CONCLUSION: Early consideration of risk, prompting evaluation of modifiable risk factors, frailty and falls risk with bone density imaging and prompt intervention may avert fracture in PLWH. Guidance on screening and lifestyle modification is available in international guidelines. Bisphosphonates are safe and effective in PLWH, with limited data for other agents.

Digital fetal scalp stimulation (dFSS) versus fetal blood sampling (FBS) to assess fetal wellbeing in labour-a multi-centre randomised controlled trial: Fetal Intrapartum Randomised Scalp Stimulation Trial (FIRSST NCT05306756).

BACKGROUND: Cardiotocography (CTG) is a screening test used to detect fetal hypoxia in labour. It has a high false positive rate resulting in many potentially unnecessary caesarean sections. Fetal blood sampling (FBS) is a second-line test of the acid-base status of the fetus. It is used to provide either reassurance that it is safe for labour to continue or objective evidence of compromise so that delivery can be expedited. Digital fetal scalp stimulation (dFSS) to elicit a fetal heart rate acceleration is an alternative less invasive second-line test of fetal wellbeing. This study aims to provide robust evidence on the role of these two second-line tests in assessing fetal wellbeing and potentially preventing operative delivery. METHODS: A multi-centre parallel group randomised controlled trial (RCT) is planned in four maternity centres in Ireland. The study aims to recruit 2500 nulliparous women with a term (≥37+0 weeks) singleton pregnancy who require a second-line test of fetal wellbeing in labour due to an abnormal CTG. Women will be allocated randomly to dFSS or FBS on a 1:1 ratio. The primary outcome is caesarean section. With 1250 women in each arm, the study will have 90% power to detect a difference of 5-6%, at a two-sided alpha significance level of 5%, assuming a caesarean section rate of at least 20% in the dFSS group. DISCUSSION: If the proposed study shows evidence that dFSS is a safe, reliable and effective alternative to FBS, this would have ground-breaking implications for labour management worldwide. It could potentially lead to a reduction in invasive procedures and emergency caesarean sections. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306756. Registered on 31 March 2022. The trial commenced enrolment on 10 May 2022. Ethical committee approval has been granted by the Research Ethics Committee (REC) of each hospital: Dublin/CWIUH REC: 12.06.2019; Cork/UCC REC: 29.11.2019; Galway/NUIG REC: 06.09.2019; Limerick/UL REC: 30.09.2019.

Predictors and Outcomes for COVID-19 Re-Admissions in the Anticipate Cohort.

Aims To describe readmissions of hospitalised patients with COVID-19, define predictors of readmission and explore the long term outcomes using the SF-12 score compared to patients who were not readmitted and those not hospitalised. Methods A single centre retrospective in North Inner-City Dublin. Recruitment was done through a COVID follow up clinic. Predictors of readmission and SF-12 scores at two timepoints post follow up at median 3 months and 12 months. Results Seventy (45%) participants were admitted, with a median age of 49.5 years (IQR 41.3-56.9), 36(51%) of whom were female. Unscheduled readmissions at ≤30 days in COVID-19 patients were 9(12.9%) and length of stay was four days (IQR 2-5). Readmissions were due to ongoing symptoms(n=9(64.3%)) or new complications(n=5(35.7%)). Mechanical ventilation and having symptoms of nausea and vomiting on index admission were predictive of readmission. (p=0.002). SF-12 scores at one year of readmitted patients were not different to patients who were never admitted at median one year follow up, p=.089. Conclusions Most readmissions were of short duration. Early follow up of patients post MV or who had nausea and vomiting on index admission should be prioritised. Wellbeing of readmitted patients was not different to those never hospitalised, at one year.

Graves' disease associated with HIV disease and late immune reconstitution inflammatory syndrome following the initiation of antiretroviral therapy.

SUMMARY: Both human immunodeficiency virus (HIV) and antiretroviral therapy (ART) are associated with endocrine dysfunction (1). The term 'immune reconstitution inflammatory syndrome' (IRIS) describes an array of inflammatory conditions that occur during the return of cell-mediated immunity following ART. Graves' disease (GD) occurs rarely as an IRIS following ART. In this study, we describe the case of a 40-year-old Brazilian female who was diagnosed with HIV following admission with cryptococcal meningitis and salmonellosis. At this time, she was also diagnosed with adrenal insufficiency. Her CD4 count at diagnosis was 17 cells/µL which rose to 256 cells/µL over the first 3 months of ART. Her HIV viral load, however, consistently remained detectable. When viral suppression was finally achieved 21 months post diagnosis, an incremental CD4 count of 407 cells/µL over the following 6 months ensued. Subsequently, she was diagnosed with a late IRIS to cryptococcus 32 months following initial ART treatment, which manifested as non-resolving lymphadenitis and resolved with high-dose steroids. Following the initiation of ART for 45 months, she developed symptomatic Graves' hyperthyroidism. At this time, her CD4 count had risen to 941 cells/µL. She has been rendered euthyroid on carbimazole. This case serves to remind us that GD can occur as an IRIS post ART and typically has a delayed presentation. LEARNING POINTS: Endocrinologists should be aware of the endocrine manifestations of HIV disease, in particular, thyroid pathology. Endocrinologists should be aware that IRIS can occur following the initiation of ART. Thyroid dysfunction can occur post ART of which Graves' disease (GD) is the most common thyroid manifestation. GD as a manifestation of ART-induced IRIS can have a delayed presentation. Infectious disease physicians should be aware of endocrine manifestations associated with HIV and ART.

Placental growth factor in assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a stepped wedge cluster randomised control trial (PARROT Ireland).

OBJECTIVE: To determine whether the addition of placental growth factor (PlGF) measurement to current clinical assessment of women with suspected pre-eclampsia before 37 weeks' gestation would reduce maternal morbidity without increasing neonatal morbidity. DESIGN: Stepped wedge cluster randomised control trial from 29 June 2017 to 26 April 2019. SETTING: National multisite trial in seven maternity hospitals throughout the island of Ireland PARTICIPANTS: Women with a singleton pregnancy between 20+0 to 36+6 weeks' gestation, with signs or symptoms suggestive of evolving pre-eclampsia. Of the 5718 women screened, 2583 were eligible and 2313 elected to participate. INTERVENTION: Participants were assigned randomly to either usual care or to usual care plus the addition of point-of-care PlGF testing based on the randomisation status of their maternity hospital at the time point of enrolment. MAIN OUTCOMES MEASURES: Co-primary outcomes of composite maternal morbidity and composite neonatal morbidity. Analysis was on an individual participant level using mixed-effects Poisson regression adjusted for time effects (with robust standard errors) by intention-to-treat. RESULTS: Of the 4000 anticipated recruitment target, 2313 eligible participants (57%) were enrolled, of whom 2219 (96%) were included in the primary analysis. Of these, 1202 (54%) participants were assigned to the usual care group, and 1017 (46%) were assigned the intervention of additional point-of-care PlGF testing. The results demonstrate that the integration of point-of-care PlGF testing resulted in no evidence of a difference in maternal morbidity-457/1202 (38%) of women in the control group versus 330/1017 (32%) of women in the intervention group (adjusted risk ratio (RR) 1.01 (95% CI 0.76 to 1.36), P=0.92)-or in neonatal morbidity-527/1202 (43%) of neonates in the control group versus 484/1017 (47%) in the intervention group (adjusted RR 1.03 (0.89 to 1.21), P=0.67). CONCLUSIONS: This was a pragmatic evaluation of an interventional diagnostic test, conducted nationally across multiple sites. These results do not support the incorporation of PlGF testing into routine clinical investigations for women presenting with suspected preterm pre-eclampsia, but nor do they exclude its potential benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881073.

A multidisciplinary evaluation of suspected, non-confirmed cases of COVID-19 including chest CT, as compared to World Health Organization recommendations.

AIM: To report an audit of the evaluation of suspected, unconfirmed cases of COVID-19 including chest computed tomography (CT), as compared to World Health Organization recommendations. METHODS: A clinical audit was undertaken examining the evaluation of patients with suspected COVID-19 with negative SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) results, with comparison to WHO recommendations. A retrospective chart review was undertaken for 90 patients examining investigations, in particular CT, used to clarify the diagnosis. RESULTS: Ninety patients underwent additional investigation. Seventy-five per cent adherence to WHO recommendations was observed. Fifty-two men (57.78%) and 38 (42.22%) women were investigated, with a median age of 69 years (range 20-96 years). Seventy-nine chest CT examinations demonstrated positive, indeterminate, and negative rates for COVID-19 of 3.79%, 24.1%, and 72.15% respectively. Three patients had discordant swab results with initially negative and subsequently positive results for SARS-CoV-2, resulting in false-negative rates of 5.1% for those retested. Combining discordant RT-PCR swab results, positive radiology, and patients treated as COVID-19-positive due to indeterminate radiology and highly consistent symptoms, resulted in a false-negative rate for initial SARS-CoV-2 RT-PCR swabs of 16.67%. CONCLUSION: Seventy-five per cent compliance with relevant WHO guidance and a false-negative rate for initial swabs of 16.67% was demonstrated. Further evidence is needed to fully determine the utility of chest CT in the diagnosis of COVID-19 in the context of initial false-negative RT-PCR results.

Antiretroviral treatment outcomes among late HIV presenters initiating treatment with integrase inhibitors or protease inhibitors.

OBJECTIVES: The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS: We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts < 200 cells/µL and/or AIDS-defining disease when starting first-line ART. Proportions of those discontinuing ART were compared using univariate analysis. Virological response was analysed using the Food & Drug Administration (FDA) snapshot analysis (HIV-1 RNA < 50 HIV-1 RNA copies/mL at week 48). RESULTS: Two hundred and eighteen late presenters were included in the study: 13.8% were women and 23.8% were of non-European ethnicity, and the mean baseline CD4 count was 91 cells/µL (standard deviation 112 cells/µL). A total of 131 late presenters started on INI- and 87 on PI-based treatment. It was found that 86.1% of patients treated with INIs and 81.1% of patients treated with PIs had a viral load < 50 copies/mL at week 48; proportions of discontinuation because of adverse events were 6.1% in the INI group and 11.5% in the PI group. No significant differences in discontinuation proportions were observed at week 12 or 48 between INI- and PI-based regimens (P = 0.76 and 0.52, respectively). Virological response was equally good in those receiving INIs and those receiving PIs (86.1% vs. 81.1%, respectively; P = 0.36). CONCLUSIONS: In a European cohort of late presenters starting first-line INI or PI-based ART regimens, there were no significant differences in discontinuation proportions or virological response at week 48.

2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0.

BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years. GUIDELINE HIGHLIGHTS: The 2019 Guidelines were extended with a new section focusing on drug-drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment-naïve PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two-drug regimen with dolutegravir and lamivudine, and a three-drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10-year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included. CONCLUSIONS: The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web-based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish.

Sonographic markers of fetal adiposity and risk of Cesarean delivery.

OBJECTIVE: Increased fetal size is associated with shoulder dystocia during labor and subsequent need for assisted delivery. We sought to investigate if increased fetal adiposity diagnosed sonographically in late pregnancy is associated with increased risk of operative delivery. METHODS: This secondary analysis of the Genesis Study recruited 2392 nulliparous women with singleton pregnancy in cephalic presentation, in a prospective, multicenter study, to examine prenatal and intrapartum predictors of Cesarean delivery. Participants underwent ultrasound and clinical evaluation between 39 + 0 and 40 + 6 weeks' gestation. Data on fetal biometry were not revealed to patients or to their managing clinicians. A fetal adiposity composite of fetal thigh adiposity and fetal abdominal wall thickness was compiled for each infant in order to determine whether fetal adiposity > 90th centile was associated with an increased risk of Cesarean or operative vaginal delivery. RESULTS: After exclusions, data were available for 2330 patients. Patients with a fetal adiposity composite > 90th centile had a higher maternal body mass index (BMI) (25 ± 5 kg/m2 vs 24 ± 4 kg/m2 ; P = 0.005), birth weight (3872 ± 417 g vs 3585 ± 401 g; P < 0.0001) and rate of induction of labor (47% (108/232) vs 40% (834/2098); P = 0.048) than did those with an adiposity composite ≤ 90th centile. Fetuses with adiposity composite > 90th centile were more likely to require Cesarean delivery than were those with adiposity composite ≤ 90th centile (P < 0.0001). After adjusting for birth weight, maternal BMI and need for induction of labor, fetal adiposity > 90th centile remained a risk factor for Cesarean delivery (P < 0.0001). A fetal adiposity composite > 90th centile was more predictive of the need for unplanned Cesarean delivery than was an estimated fetal weight > 90th centile (odds ratio, 2.20 (95% CI, 1.65-2.94; P < 0.001) vs 1.74 (95% CI, 1.29-2.35; P < 0.001). Having an adiposity composite > 90th centile was not associated with an increased likelihood of operative vaginal delivery when compared with having an adiposity composite ≤ 90th centile (P = 0.37). CONCLUSIONS: Fetuses with increased adipose deposition are more likely to require Cesarean delivery than are those without increased adiposity. Consideration should, therefore, be given to adding fetal thigh adiposity and abdominal wall thickness to fetal sonographic assessment in late pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Effect of exercise modality on markers of insulin sensitivity and blood glucose control in pregnancies complicated with gestational diabetes mellitus: a systematic review.

BACKGROUND/AIM: Exercise can be used as a strategy to attenuate hyperglycaemia experienced during gestational diabetes mellitus (GDM). To maximize its use for clinical management, the most effective modality should be identified. The purpose of this review is to elucidate the most effective modality of exercise on insulin sensitivity and blood glucose control in pregnant women with or at risk of GDM. METHODS: A search was undertaken in MEDLINE, PubMed, Scopus, CINAHL, the Cochrane Library, Embase and the Maternity & Infant Healthcare Database. Studies that met inclusion criteria were randomized controlled trials and case-controlled studies, which compared exercise interventions with standard care during pregnancy in women with or at risk of GDM. RESULTS: Two interventions using resistance training, eight using aerobic exercise and two using a combination of both modalities were included. The interventions showed consistently that requirements of insulin therapy, dosage, and latency to administration were improved in the exercise groups. Less consistent results were observed for capillary blood glucose measurements; however, both modalities and combination of modalities were effective at improving blood glucose control in already diagnosed patients and pregnant women with obesity. Discrepancies in the timing of intervention, GDM diagnostic criteria, and the different measures used to assess glucose metabolism make it difficult to draw clear recommendations. CONCLUSION: Exercising three times per week for 40-60 min at 65-75% age-predicted heart rate maximum using cycling, walking or circuit training as a modality improved glycaemic control in GDM patients and reduced incidence of GDM in pregnant women with obesity. Further studies looking specifically at the effects of different modalities of exercise on glucose metabolism with combined strategies to enhance insulin sensitivity should be explored to maximize benefits for GDM pregnancies. Consistency in design and delivery of exercise-only interventions is required to make recommendations on a suitable exercise prescription in this population. In practice, adherence to consensus in diagnostic cut-offs for GDM diagnosis is fundamental for standardizing future research.

Suicide risk assessment in Australian emergency departments: assessing clinicians' disposition decisions.

Objective. To determine (1) the uniformity of disposition decisions made by clinicians working in Australian emergency departments (EDs) using vignettes describing patients presenting with deliberate self-harm or suicide risk; (2) factors associated with these decisions; (3) factors associated with confidence in these decisions. Methodology. We validated and distributed by email an online survey tool to Australian emergency clinicians via their colleges. Participants were presented with five vignettes and asked to rate the level of risk and protective factors for suicide, the patient's disposition (admit/discharge/review), factors influencing this decision, their confidence in the decision, and factors that would have improved their confidence. Results. Percentages of participants choosing the modal disposition decision for each scenario ranged from 58.6% (136/232) to 92.4% (220/238), demonstrating uniformity in clinicians' disposition decisions. Predictors of disposition were consistently level of risk factors perceived and, infrequently, clinician factors including age and years experience. Confidence in disposition decisions was high across scenarios. Clinicians reported patient, clinician, contextual and decision support factors relevant to an Australian emergency context affected their disposition decisions and confidence in decisions. Conclusion. Emergency clinicians are uniform and confident in their disposition decisions for patient vignettes where there is risk of suicide or self harm.

Vitamin D status and parathyroid hormone relationship in adolescents and its association with bone health parameters: analysis of the Northern Ireland Young Heart's Project.

UNLABELLED: In girls, a plateau in parathyroid hormone (PTH) was observed at a 25-hydroxyvitamin D (25(OH)D) concentration of approximately 60 nmol/l. In boys, there was no plateau in PTH concentrations as 25(OH)D concentration increased. A 25(OH)D threshold of 60 nmol/l appears to have implications for bone health outcomes in both girls and boys. INTRODUCTION: Our objective was to investigate if there is a threshold 25(OH)D concentration where a plateau in PTH concentration is evident and to examine the impact of this relationship on bone mineral density (BMD) and bone turnover in a representative sample of adolescents. METHODS: We conducted a cross-sectional analysis among 1,015 Northern Irish adolescents aged 12 and 15 years. Serum 25(OH)D, PTH, osteocalcin, type 1 collagen cross-linked C-telopeptide (CTx), and BMD of the nondominant forearm and heel were measured. Nonlinear regression analysis was used to model the association between 25(OH)D and PTH. RESULTS: In girls, a plateau in PTH was observed at a 25(OH)D concentration of approximately 60 nmol/l (PTH = 47.146 + 370.314 x exp((-0.092 x 25(OH)D))) while no plateau in PTH was observed in boys (PTH = 42.144 + 56.366 x exp((-0.022 x 25(OH)D))). Subjects with 25(OH)D levels <60 nmol/l had significantly higher osteocalcin concentrations (P < 0.05) compared with those who had >or=60 nmol/l, while no significant (P > 0.05) differences were noted for CTx concentrations. In girls only, nondominant forearm BMD but not heel BMD was significantly higher (P = 0.046) in those with 25(OH)D concentrations >or= 60 nmol/l. CONCLUSIONS: Serum 25(OH)D levels above 60 nmol/l in Northern Irish adolescent girls prevent an increase in serum PTH levels and maintaining 25(OH)D >60 nmol/l in both girls and boys may lead to improved bone health outcomes.

Multicentric Castleman's disease & HIV infection.

We report the case of a 35 year patient from Nigeria who presented with fever and splenomegaly. The initial diagnosis was Salmonellosis. However, relapsing symptoms lead to a re-evaluation and ultimately a diagnosis of Multicentric Castleman's Disease (MCD). There is no gold standard treatment but our patient responded to Rituximab and Highly active anti-retroviral therapy. MCD is a rare, aggressive disease that should be considered in a HIV positive patient presenting with fever and significant lymphadenopathy.

The pool chlorine hypothesis and asthma among boys.

UNLABELLED: Swimming pool sanitation has largely been concerned with the microbiological quality of pool water, which is normally treated using a number of chlorine products. Recent studies have pointed to the potential hazards of chlorine by-products to the respiratory epithelium, particularly in indoor, poorly ventilated, pools. The aim of our study was to elucidate whether chronic exposure to indoor chlorinated swimming pools was associated with an increased likelihood of the development of asthma in boys. METHODS: The subjects were boys aged between 6 and 12 years. Data was collected by means of parental responses to a standardized asthma questionnaire (ISAAC: International Study of Asthma and Allergies in Childhood), supplemented with additional questions regarding frequency of attendance, number of years attendance, whether the child is a swimming team member. The questionnaire return rate was 71/% (n = 121). 23 boys were excluded on the basis that they had asthma before they started swimming (n = 97). There was a significant association between number of years a boy had been swimming and the likelihood of wheezing in the last 12 months (p = 0.009; OR = 1.351; 95% CI = 1.077-1.693) and diagnosed asthma (p = 0.046; OR = 1.299; 95% CI = 1.004-1.506). The greater the number the number of years a boy had been attending an indoor, chlorinated pool, the greater the likelihood of wheezing in the last 12 months or "had asthma". Age, parental smoking habits and being a swimming team member had no association with any of the asthma variables examined. Swimming pool attendance may be a risk factor in asthma in boys.

Cutaneous T-cell lymphoma presenting as a ten month history of unilateral facial swelling.

A 25-year-old fisherman presented with a ten-month history of unilateral facial swelling involving his lower lip and eyelids. The differential diagnosis for oro-facial swelling is extensive including congenital, infective, inflammatory and neoplastic processes. Biopsies revealed a cutaneous T cell lymphoma.

Effect of 17beta-oestradiol on transepithelial calcium transport in human intestinal-like Caco-2 cells and its interactions with 1,25-dihydroxycholecalciferol and 9-cis retinoic acid.

BACKGROUND: Oestrogen therapy helps prevent bone loss in postmenopausal women and corrects a decline in Ca absorption efficiency at the onset of menopause. However, the mechanism by which 17beta-oestradiol (17beta-E2) stimulates Ca absorption is unclear. Oestrogen may exert its effect indirectly via increasing 1,25-dihydroxycholeciferol (1,25 (OH)2D3) or its receptor, or act more directly on the intestines via the oestrogen receptor (OR). Since oestrogen also increases retinol levels, this may influence Ca absorption. AIM: To investigate the effect of 17beta-E2 alone and in combination with 1,25 (OH)2D3 on intestinal Ca uptake and absorption in Caco-2 cells cultured under deplete- and replete-9-cis retinoic acid (9-cis RA) conditions. METHODS: Twenty-one day-old Caco-2 cell monolayers (n 9 wells per treatment) were exposed to 9-cis RA-deplete and -replete media containing dimethyl sulfoxide (control), 10 nM-1,25 (OH)2D3, 10 nM-17beta-E2, or 10 nM-1,25 (OH)2D3 plus 10 nM-17beta-E2, for 48 h. RESULTS: 1,25 (OH)2D3 stimulated Ca uptake, total Ca transport, calbindin D(9K) and CaT1 mRNA levels, while 17beta-E2 and 9-cis RA had no effect on Ca absorption or uptake. Nor did they augment the stimulatory effect of 1,25 (OH)2D3. CONCLUSION: These in vitro findings suggest that oestrogen does not have a direct effect on intestinal Ca absorption.

Using the EM algorithm to weight data sets of unknown precision when modelling fish stocks.

Stocks of commercial fish are often modelled using sampling data of various types, of unknown precision, and from various sources assumed independent. We want each set to contribute to estimates of the parameters in relation to its precision and goodness of fit with the model. Iterative re-weighting of the sets is proposed for linear models until the weight of each set is found to be proportional to (relative weighting) or equal to (absolute weighting) the set-specific residual invariances resulting from a generalised least squares fit. Formulae for the residual variances are put forward involving fractional allocation of degrees of freedom depending on the numbers of independent observations in each set, the numbers of sets contributing to the estimate of each parameter, and the number of weights estimated. To illustrate the procedure, numbers of the 1984 year-class of North Sea cod (a) landed commercially each year, and (b) caught per unit of trawling time by an annual groundfish survey are modelled as a function of age to estimate total mortality, Z, relative catching power of the two fishing methods, and relative precision of the two sets of observations as indices of stock abundance. It was found that the survey abundance indices displayed residual variance about 29 times higher than that of the annual landings.

Brain metabolism in the cerebellum and visual cortex correlates with neuropsychological testing in patients with Alzheimer's disease.

This study was designed to measure glucose metabolic deficits in areas not typically recognized as abnormal on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans in patients with Alzheimer's disease (AD), and to correlate such findings with subtle neuropsychological impairment. FDG-PET scans on 38 AD patients with no clinical evidence of visual, spatial or motor deficits were acquired on the PET HEAD scanner 40 min following the intravenous administration of 115 microCi.kg-1 of FDG. All FDG-PET scans were analysed blindly using a region of interest (ROI) template with regions for the primary visual cortex (PVC), secondary visual cortex (SVC) and cerebellum. Counts from the ROIs of these regions were normalized to whole brain activity and the results were compared with psychometric and neuropsychological measures. A number of significant correlations were found between these structures and various neuropsychological measures (P<0.05). Specifically, there were significant correlations between clock drawing and the cerebellum activity; memory and activity in the PVC, SVC and cerebellum; social score and activity in the PVC and left cerebellum; judgement and activity in the right SVC and right PVC; and the overall Mini-Mental State Examination and activity in the PVC, SVC and cerebellum. The results of this study suggest that metabolism in areas not typically recognized as abnormal on FDG-PET scans in AD, such as the PVC, SVC and cerebellum, is correlated with deficits in neuropsychological function. This may have important clinical and pathophysiological implications in the study of AD and other illnesses of dementia.