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OBJECTIVE: To examine the effect of a new point-of-use treatment for drinking-water, a commercially developed flocculant-disinfectant, on the prevalence of diarrhoea in children. METHODS: We conducted a randomized controlled trial among 514 rural Guatemalan households, divided into 42 neighbourhood clusters, for 13 weeks, from 4 November 2002 through 31 January 2003. Clusters assigned to water treatment with the flocculant-disinfectant were compared with those using their usual water-handling practices. The longitudinal prevalence of diarrhoea was calculated as the proportion of total days with diarrhoea divided by the total number of days of observation. The prevalence of diarrhoea was compared using the Wilcoxon rank-sum test. FINDINGS: The 1702 people in households receiving the disinfectant had a prevalence of diarrhoea that was 40% lower than that among the 1699 people using standard water-handling practices (0.9% versus 1.5%; P = 0.001). In households using the flocculant-disinfectant, children < 1 year of age had a 39% lower prevalence of diarrhoea than those in households using their standard practices (3.7% versus 6.0%; P = 0.005). CONCLUSION: In settings where families rarely treat drinking-water, we introduced a novel flocculant-disinfectant that reduced the longitudinal prevalence of diarrhoea, especially among children aged < 1 year, among whom diarrhoea has been strongly associated with mortality. Successful introduction and use of this product could contribute to preventing diarrhoeal disease globally. Copyright © 2006 World Health Organization [ABSTRACT FROM AUTHOR]

Background: Microglia (MG) are myeloid cells of the central nervous system that support homeostasis and instigate neuroinflammation in pathologies. Single-cell RNA sequencing (scRNA-seq) revealed the functional heterogeneity of MG in mouse brains. Microglia are self-renewing cells and inhibition of colony-stimulating factor 1 receptor (CSF1R) signaling depletes microglia which rapidly repopulate. The functions of repopulated microglia are poorly known., Methods: We combined scRNA-seq, bulk RNA-seq, immunofluorescence, and confocal imaging to study the functionalities and morphology of repopulated microglia., Results: A CSRF1R inhibitor (BLZ-945) depleted microglia within 21 days and a number of microglia was fully restored within 7 days, as confirmed by TMEM119 staining and flow cytometry. ScRNA-seq and computational analyses demonstrate that repopulated microglia originated from preexisting progenitors and reconstituted functional clusters but upregulated inflammatory genes. Percentages of proliferating, immature microglia displaying inflammatory gene expression increased in aging mice. Morphometric analysis of MG cell body and branching revealed a distinct morphology of repopulated MG, particularly in brains of old mice. We demonstrate that with aging some repopulated MG fail to reach the homeostatic phenotype. These differences may contribute to the deterioration of MG protective functions with age., (© 2024. The Author(s).)

Photoplethysmography (PPG) signals have become a key technology in many fields, such as medicine, well-being, or sports. Our work proposes a set of pipelines to extract remote PPG signals (rPPG) from the face robustly, reliably, and configurably. We identify and evaluate the possible choices in the critical steps of unsupervised rPPG methodologies. We assess a state-of-the-art processing pipeline in six different datasets, incorporating important corrections in the methodology that ensure reproducible and fair comparisons. In addition, we extend the pipeline by proposing three novel ideas; 1) a new method to stabilize the detected face based on a rigid mesh normalization; 2) a new method to dynamically select the different regions in the face that provide the best raw signals, and 3) a new RGB to rPPG transformation method, called Orthogonal Matrix Image Transformation (OMIT) based on QR decomposition, that increases robustness against compression artifacts. We show that all three changes introduce noticeable improvements in retrieving rPPG signals from faces, obtaining state-of-the-art results compared with unsupervised, non-learning-based methodologies and, in some databases, very close to supervised, learning-based methods. We perform a comparative study to quantify the contribution of each proposed idea. In addition, we depict a series of observations that could help in future implementations.

Background: Postnatal depression (PND) affects over 12% of mothers, with numbers rising during COVID-19. Singing groups can support mothers with PND; however, online delivery has never been evaluated. SHAPER-PNDO, a single-arm clinical trial, evaluated the feasibility, clinical efficacy, and well-being outcomes of a 6-week online version of Breathe Melodies for Mums (M4M) singing intervention developed for mothers with PND during COVID-19 lockdowns., Methods: The primary objective of this study was to assess the feasibility of a group online singing intervention for new mothers with postnatal depression. This was ascertained through recruitment rates, study retention rates, attendance rates to the singing sessions, and study completion rates. The secondary objective of the study was to assess the clinical efficacy and well-being outcomes of the singing intervention. Specifically, we measured change in Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Office for National Statistics Wellbeing Scale (ONS) scores from baseline to end-of-intervention (week 6); follow-up assessments were completed at weeks 3, 16, and 32. Mothers were eligible if they scored ≥10 on the baseline EPDS., Results: Eighty-seven percent of the 37 recruited mothers completed the study, attending, on average, 5 of the 6 group singing sessions. With regard to secondary outcomes, at end-of-treatment, mothers experienced significant reductions in depression (EPDS, 16.6 ± 3.7 to 11.2 ± 5.3, 95% CI [0.79,1.65]), anxiety (STAI-S, 48.4 ± 27.1 to 41.7 ± 26.8, 95% CI [4.96, 17.65]) and stress (PSS, 29.0 ± 5.7 to 19.7 ± 5.3, 95% CI [1.33, 7.07]); and, furthermore, significant improvements in life satisfaction (ONS, 50.5 ± 23.0 to 72.8 ± 11.7, 95% CI [- 39.86, - 4.64]) and feelings of worthwhileness (ONS, 51.7 ± 30.4 to 78.6 ± 15.1, 95% CI [- 52.79, - 0.85]). Reduction on the EPDS correlated with a reduction on the BDI and the STAI-S and maternal childhood maltreatment was predictive of a smaller treatment response., Conclusions: M4M online was feasible to mothers who partook in the programme. Furthermore, M4M online supports the mental health and well-being of new mothers experiencing PND, especially when barriers to in-person treatment are present., Trial Registration: ClinicalTrials.gov NCT04857593 . Registered 22 April 2021, retrospectively registered., (© 2023. The Author(s).)

In biomedical engineering, deep neural networks are commonly used for the diagnosis and assessment of diseases through the interpretation of medical images. The effectiveness of these networks relies heavily on the availability of annotated datasets for training. However, obtaining noise-free and consistent annotations from experts, such as pathologists, radiologists, and biologists, remains a significant challenge. One common task in clinical practice and biological imaging applications is instance segmentation. Though, there is currently a lack of methods and open-source tools for the automated inspection of biomedical instance segmentation datasets concerning noisy annotations. To address this issue, we propose a novel deep learning-based approach for inspecting noisy annotations and provide an accompanying software implementation, AI 2 Seg, to facilitate its use by domain experts. The performance of the proposed algorithm is demonstrated on the medical MoNuSeg dataset and the biological LIVECell dataset.

Background: Postnatal depression (PND) affects 13% of new mothers, with numbers rising during the COVID-19 pandemic. Despite this prevalence, many women have difficulty with or hesitancy towards accessing pharmacological and/or psychological interventions. Group-based mother-baby activities, however, have a good uptake, with singing improving maternal mental health and the mother-infant relationship. The recent lockdowns highlight the importance of adapting activities to an online platform that is wide-reaching and accessible., Aims: The SHAPER-PNDO study will primarily analyse the feasibility of a 6-week online singing intervention, Melodies for Mums (M4M), for mothers with PND who are experiencing barriers to treatment. The secondary aim of the SHAPER-PNDO study will be to analyse the clinical efficacy of the 6-week M4M intervention for symptoms of postnatal depression., Methods: A total of 120 mothers and their babies will be recruited for this single-arm study. All dyads will attend 6 weekly online singing sessions, facilitated by Breathe Arts Health Research. Assessments will be conducted on Zoom at baseline and week 6, with follow-ups at weeks 16 and 32, and will contain interviews for demographics, mental health, and social circumstances, and biological samples will be taken for stress markers. Qualitative interviews will be undertaken to understand the experiences of women attending the sessions and the facilitators delivering them. Finally, data will be collected on recruitment, study uptake and attendance of the programme, participant retention, and acceptability of the intervention., Discussion: The SHAPER-PNDO study will focus on the feasibility, alongside the clinical efficacy, of an online delivery of M4M, available to all mothers with PND. We hope to provide a more accessible, effective treatment option for mothers with PND that can be available both during and outside of the pandemic for mothers who would otherwise struggle to attend in-person sessions, as well as to prepare for a subsequent hybrid RCT., Trial Registration: ClinicalTrials.gov Identifier: NCT04857593 . Registered retrospectively on 22 April 2021. The first participants were recruited on 27 January 2021, and the trial is ongoing., (© 2022. The Author(s).)

Cancer remains a primary cause of morbidity and mortality worldwide, and its incidence continues to increase. The most common cause of death in cancer patients is tumour recurrence. Surgery is the gold standard in the treatment of most tumours. However, cancer surgery can lead to the release of tumour cells into the systemic circulation. Surgical stress and several perioperative factors have been suggested to boost tumour growth, thereby increasing the risk of metastatic recurrence. Preclinical and clinical studies suggest that anaesthetics and adjuvants administered during the perioperative period may impact cancer recurrence and survival. This document summarises the current evidence regarding the effects of anaesthetic drugs and analgesic techniques on the immune system, systemic inflammatory response and tumour cells, as well as their impact on cancer recurrence., (© the authors; licensee ecancermedicalscience.)

NiFe and CoFe (MFe) layered double hydroxides (LDHs) are among the most active electrocatalysts for the alkaline oxygen evolution reaction (OER). Herein, we combine electrochemical measurements, operando X-ray scattering and absorption spectroscopy, and density functional theory (DFT) calculations to elucidate the catalytically active phase, reaction center and the OER mechanism. We provide the first direct atomic-scale evidence that, under applied anodic potentials, MFe LDHs oxidize from as-prepared α-phases to activated γ-phases. The OER-active γ-phases are characterized by about 8% contraction of the lattice spacing and switching of the intercalated ions. DFT calculations reveal that the OER proceeds via a Mars van Krevelen mechanism. The flexible electronic structure of the surface Fe sites, and their synergy with nearest-neighbor M sites through formation of O-bridged Fe-M reaction centers, stabilize OER intermediates that are unfavorable on pure M-M centers and single Fe sites, fundamentally accounting for the high catalytic activity of MFe LDHs.

Purpose: To determine the impact of altering dietary sodium intake for 3 days preceding exercise on sweat sodium concentration [Na + ], and cardiovascular and thermoregulatory variables., Methods: Fifteen male endurance athletes (runners n = 8, cyclists n = 7) consumed a low (LNa, 15 mg kg -1  day -1 ) or high (HNa, 100 mg kg -1  day -1 ) sodium diet, or their usual free-living diet [UDiet, 46 (37-56) mg kg -1  day -1 ] for 3 days in a double-blind, randomized cross-over design, collecting excreted urine (UNa) and refraining from exercise. On day 4, they completed 2 h running at 55% [Formula: see text]O 2max or cycling at 55% maximum aerobic power in T amb 35 °C. Pre- and post-exercise blood samples were collected, and sweat from five sites using absorbent patches along the exercise protocol., Results: UNa on days 2-3 pre-exercise [mean (95% CI) LNa 16 (12-19) mg kg -1  day -1 , UDiet 46 (37-56) mg kg -1  day -1 , HNa 79 (72-85) mg kg -1  day -1 ; p < 0.001] and pre-exercise aldosterone [LNa 240 (193-286) mg kg -1  day -1 , UDiet 170 (116-224) mg kg -1  day -1 , HNa 141 (111-171) mg kg -1  day -1 ; p = 0.001] reflected sodium intake as expected. Pre-exercise total body water was greater following HNa compared to LNa (p < 0.05), but not UDiet. Estimated whole-body sweat [Na + ] following UDiet was 10-11% higher than LNa and 10-12% lower than HNa (p < 0.001), and correlated with pre-exercise aldosterone (1st h r =  - 0.568, 2nd h r =  - 0.675; p < 0.01). Rectal temperature rose more quickly in LNa vs HNa (40-70 min; p < 0.05), but was similar at the conclusion of exercise, and no significant differences in heart rate or perceived exertion were observed., Conclusions: Three day altered sodium intake influenced urinary sodium excretion and sweat [Na + ], and the rise in rectal temperature, but had no effect on perceived exertion during moderate-intensity exercise in hot ambient conditions.

Automatic medical diagnosis is an emerging center of interest in computer vision as it provides unobtrusive objective information on a patient's condition. The face, as a mirror of health status, can reveal symptomatic indications of specific diseases. Thus, the detection of facial abnormalities or atypical features is at upmost importance when it comes to medical diagnostics. This survey aims to give an overview of the recent developments in medical diagnostics from facial images based on computer vision methods. Various approaches have been considered to assess facial symptoms and to eventually provide further help to the practitioners. However, the developed tools are still seldom used in clinical practice, since their reliability is still a concern due to the lack of clinical validation of the methodologies and their inadequate applicability. Nonetheless, efforts are being made to provide robust solutions suitable for healthcare environments, by dealing with practical issues such as real-time assessment or patients positioning. This survey provides an updated collection of the most relevant and innovative solutions in facial images analysis. The findings show that with the help of computer vision methods, over 30 medical conditions can be preliminarily diagnosed from the automatic detection of some of their symptoms. Furthermore, future perspectives, such as the need for interdisciplinary collaboration and collecting publicly available databases, are highlighted.

Postoperative shivering is a common complication of anaesthesia. Shivering is believed to increase oxygen consumption, increase the risk of hypoxemia, induce lactic acidosis, and catecholamine release. Therefore, it might increase the postoperative complications especially in high-risk patients. Moreover, shivering is one of the leading causes of discomfort for postsurgical patients. Shivering is usually triggered by hypothermia. However, it occurs even in normothermic patients during the perioperative period. The aetiology of shivering has been understood insufficiently. Another potential mechanism is pain and acute opioid withdrawal (especially with the use of short-acting narcotics). Besides that shivering is poorly understood, the gold standard for the treatment and prevention has not been defined yet. Perioperative hypothermia prevention is the first method to avoid shivering. Many therapeutic strategies for treating shivering exist and most are empiric. Unfortunately, the overall quality of the antishivering guidelines is low. Two main strategies are available: pharmacological and non-pharmacological antishivering methods. The combination of forced-air warming devices and intravenous meperidine is the most validated method. We also analysed different medications but final conclusion about the optimal antishivering medication is difficult to be drawn due to the lack of high-quality evidence. Nevertheless, control of PS is possible and clinically effective with simple pharmacological interventions combined with non pharmacological methods. However, to be consistent with the most up-to-date, evidence-based practice, future antishivering treatment protocols should optimize methodological rigor and transparency., Competing Interests: Conflict of interest Nothing to declare

Bodily awareness is a central component of human sensation, action, and cognition. The human body is subject to profound changes over the adult lifespan. We live in an aging society: the mean age of people living in industrialized countries is currently over 40 years, and further increases are expected. Nevertheless, there is a lack of comprehensive knowledge that links changes in embodiment that occur with age to neuronal mechanisms and associated sensorimotor and cognitive deficits in older adults. Here, we synthesize existing evidence and introduce the NFL Framework of Embodied Aging, which links basic neuronal (N) mechanisms of age-related sensorimotor decline to changes in functional (F) bodily impairments, including deficits in higher-level cognitive functions, and impairments in daily life (L). We argue that cognitive and daily life impairments associated with old age are often due to deficits in embodiment, which can partly be linked to neuronal degradation at the sensorimotor level. The framework may encourage the development of novel approaches to improve autonomous living for older adults., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Kinship Face in the Wild data sets, recently published in TPAMI, are currently used as a benchmark for the evaluation of kinship verification algorithms. We recommend that these data sets are no longer used in kinship verification research unless there is a compelling reason that takes into account the nature of the images. We note that most of the image kinship pairs are cropped from the same photographs. Exploiting this cropping information, competitive but biased performance can be obtained using a simple scoring approach, taking only into account the nature of the image pairs rather than any features about kin information. To illustrate our motives, we provide classification results utilizing a simple scoring method based on the image similarity of both images of a kinship pair. Using simply the distance of the chrominance averages of the images in the Lab color space without any training or using any specific kin features, we achieve performance comparable to state-of-the-art methods. We provide the source code to prove the validity of our claims and ensure the repeatability of our experiments.

We have previously demonstrated a crucial role of nuclear protein 1 (NUPR1) in tumor development and progression. In this work, we report the functional characterization of a novel Nupr1-like isoform (NUPR1L) and its functional interaction with the protumoral factor NUPR1. Through the use of primary sequence analysis, threading, and homology-based molecular modeling, as well as expression and immunolocalization, studies reveal that NUPR1L displays properties, which are similar to member of the HMG-like family of chromatin regulators, including its ability to translocate to the cell nucleus and bind to DNA. Analysis of the NUPR1L promoter showed the presence of two p53-response elements at positions -37 and -7, respectively. Experiments using reporter assays combined with site-directed mutagenesis and using cells with controllable p53 expression demonstrate that both of these sequences are responsible for the regulation of NUPR1L expression by p53. Congruently, NUPR1L gene expression is activated in response to DNA damage induced by oxaliplatin treatment or cell cycle arrest induced by serum starvation, two well-validated methods to achieve p53 activation. Interestingly, expression of NUPR1L downregulates the expression of NUPR1, its closely related protumoral isoform, by a mechanism that involves the inhibition of its promoter activity. At the cellular level, overexpression of NUPR1L induces G1 cell cycle arrest and a decrease in their cell viability, an effect that is mediated, at least in part, by downregulating NUPR1 expression. Combined, these experiments constitute the first functional characterization of NUPR1L as a new p53-induced gene, which negatively regulates the protumoral factor NUPR1., (© 2015 Wiley Periodicals, Inc.)

Nupr1 is a chromatin protein, which cooperates with Kras(G12D) to induce PanIN formation and pancreatic cancer development in mice, though the molecular mechanisms underlying this effect remain to be fully characterized. In the current study, we report that Nupr1 acts as a gene modifier of the effect of Kras(G12D)-induced senescence by regulating Dnmt1 expression and consequently genome-wide levels of DNA methylation. Congruently, 5-aza-2'-deoxycytydine, a general inhibitor of DNA methylation, reverses the Kras(G12D)-induced PanIN development by promoting senescence. This requirement of Nupr1 expression, however, is not restricted to the pancreas since in lung of Nupr1(-/-) mice the expression of Kras(G12D) induces senescence instead of transformation. Therefore, mechanistically this data reveals that epigenetic events, at least at the level of DNA methylation, modulate the functional outcome of common genetic mutations, such as Kras(G12D), during carcinogenesis. The biomedical relevance of these findings lies in that they support the rational for developing similar therapeutic interventions in human aimed at controlling either the initiation or progression of cancer.

Pancreatic Ductal Adenocarcinoma (PDAC) is a disease with a great heterogeneity in the response to treatments. To improve the responsiveness to treatments there are two different approaches, the first one consist to develop new and more efficient drugs that intent to cure all patients and the second one is to use already-approved drugs, alone or in combination, but selecting beforehand the most sensitive patients. In this work we explored the efficiency of the second possibility. We developed a collection of 17 PDAC samples collected by Endoscopic Ultrasound-Guided Fine-Needle Aspiration (EUS-FNA) or surgery and preserved as xenografts and as primary cultures. This collection was characterized at molecular level by a transcriptomic analysis using an Affymetrix approach. In this paper we present data demonstrating that a subgroup of PDAC responds to low doses of 5-aza-dC. These tumors show a specific RNA expression profile that could serve as a marker, but there is no correlation with Dnmt1, Dnmt3A or Dnmt3B expression. Responder tumors corresponded to well-differentiated samples and longer survival patients. In conclusion, we present data obtained with the well-known drug 5-aza-dC as a proof of concept that a drug that seems to be inefficient in solid tumors in general could be applicable to a particular subgroup of patients with PDAC.

Cholinergic signaling is thought to be involved in morphine dependence and withdrawal, but the specific mechanisms involved remain unclear. The current study aimed to identify alterations in the cholinergic system that may contribute to the development of morphine dependence and withdrawal. Acetylcholinesterase (AChE) activity and [³H]-epibatidine binding were evaluated in order to determine if morphine dependence and withdrawal induces alterations in cholinergic signaling or expression of high affinity nicotinic acetylcholine receptors (nAChRs) in the midbrain (MB), medial habenula (MHb) and interpeduncular nucleus (IPN). The effect of cholinergic signaling through nAChRs on morphine-withdrawal induced jumping behavior was then determined. Lastly, the contribution of β4-containing nAChRs receptors in the MHb to morphine-withdrawal induced jumping behavior and neuronal activity as indicated by c-fos expression was assessed. Chronic morphine administration decreased AChE activity in MB and MHb, an effect that was no longer present following precipitated withdrawal. Morphine dependent mice showed increased nicotinic acetylcholine receptor (nAChR) levels in MB. Further, nicotine (0.4 mg/kg) and lobeline (3 mg/kg) decreased jumping behavior while mecamylamine (1 mg/kg) had no effect. Knock-down of β4 subunit-containing nAChRs in the MHb attenuated c-fos activation, but did not decrease morphine withdrawal-induced jumping. Thus, morphine withdrawal induces cholinergic signaling in the MHb, but this does not appear to be responsible for the effects of cholinergic drugs on somatic signs of opiate withdrawal, as measured by jumping behavior., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A specific fatty acid binding protein was isolated from Giardia lamblia, using an affinity column with butyric acid acting as a ligand in place of stearic acid. This method has proved to be more efficient than the one previously described using stearic acid as ligand. The purified fraction showed 8 electrophoretic bands of proteins, with molecular weights ranging between 8 and 80 kDa. This pattern is a consequence of the aggregation of a protein with a molecular weight of 8,215 Da, corresponding to the lower molecular weight band, the only one capable of binding to fatty acids. The labeled oleic acid bound to these purified proteins was replaced by a 100-fold greater concentration of taurocholate, glycocholate, deoxycholate, palmitic acid, and arachidonic acid, having a greater displacement of the bile salts than the free fatty acids.

We evaluated enteric infection serology as an alternative outcome measure to diarrhea prevalence in a randomized controlled trial of household-based drinking water treatment; 492 households were randomly assigned to 5 household-based water treatment interventions or control. Individuals were followed weekly over 52 weeks to measure diarrhea prevalence. Study subjects of age

Unlabelled: The thyroid carcinoma (TC) is not very frequent among all cancers. Its course is slow and is high potentially curable. Our aim was to analyse the characteristics in patients with TC. A retrospective analysis on 171 patients, with an average age of 41.1 (+/- 14.6), who asked for TC to our service between the years 2000-04, was performed. From case histories it was evaluated: anamnesis, diagnostic image, histopathology and evolution. Tumours were grouped for size and TNM (tumour-nodule-metastasis) in stages (S). A stimulated serum thyroglobulin level >2 ng/ml and positive image with 131I or another nuclear marker were considered as positive for residual TC. In the totality of the analyzed patients 88% were female, 62% below 45 years old, and in 77% the thyroid function was normal. The fine needle aspiration (FNA) was diagnostic in 78%. Papillary thyroid carcinoma (PTC) in 96%. The 63% was SI; 14% SII; 19% SIII and 4% SIV. During follow-up, we observed that 90% of patients with Tg between 2 and 10 had evidence of residual TC, and 100% with Tg >10 ng/ml, whereas 18% of those whose stimulated Tg <2 presented positive image. There was not found significative correlation with pathologic antecedents or relevant image signs., In Conclusion: TCP was the most frequent carcinoma in women, in patients younger than 45 years and in those who have euthyroid function. A stimulated serum thyroglobulin level was a good indicator for residual TC, but failed to select those patients who were disease free.

Regulators of G-protein signalling (RGS) proteins are a recently discovered class of proteins that modulate G-protein activity. More than 20 RGS proteins have been identified and are expressed throughout the body and brain. In particular, RGS4 appears to regulate dopamine receptor function and has been implicated in several dopamine related diseases, including schizophrenia. This study presents an extensive examination of the regional distribution of RGS4 mRNA in postmortem human brain. Using in situ hybridization, the expression levels of RGS4 mRNA were determined in human hemicoronal (Talairach sections +8 and -20) brain sections. In the rostral slice (Talairach +8) highest levels were found in the inferior frontal cortex, the superior frontal, and the cingulate cortex. Slightly lower levels were found in the insular cortex and inferior temporal cortex. The caudate, putamen and nucleus accumbens had lower levels. In the caudal slice (-20), the cortical layers showed the highest levels, with moderate levels observed in the parahippocampal gyrus, low levels in the CA-pyramidal region, and almost undetectable levels in the thalamus. In the frontal cortex a dense band was apparent near one of the inner layers of the cortex. In conclusion, RGS4 mRNA distribution in human postmortem tissue from normal persons was very dense in most cortical layers examined, with lower density in the basal ganglia and thalamus.

Water and sanitation interventions in developing countries have historically been difficult to evaluate. We conducted a seroepidemiologic study with the following goals: 1) to determine the feasibility of using antibody markers as indicators of waterborne pathogen infection in the evaluation of water and sanitation intervention projects; 2) to characterize the epidemiology of waterborne diarrheal infections in rural Guatemala, and 3) to measure the age-specific prevalence of antibodies to waterborne pathogens. Between September and December 1999, all children 6-36 months of age in 10 study villages were invited to participate. We collected sufficient serum from 522 of 590 eligible children, and divided them into six-month age groups for analysis (6-12, 13-18, 19-24, 25-30, and 31-36 months). The prevalence of antibodies was lowest in children 6-12 months old compared with the four older age groups for the following pathogens: enterotoxigenic Escherichia coli (48%, 81%, 80%, 77%, and 83%), Norwalk virus (27%, 61%, 83%, 94%, and 94%), and Cryptosporidium parvum (27%, 53%, 70%, 67%, and 73%). The prevalence of total antibody to hepatitis A virus increased steadily in the three oldest age groups (40%, 28%, 46%, 60%, and 76%). In contrast, the prevalence of antibody to Helicobacter pylori was relatively constant in all five age groups (20%, 19%, 21%, 25%, and 25%). Serology appears to be an efficient and feasible approach for determining the prevalence of infection with selected waterborne pathogens in very young children. Such an approach may provide a suitable, sensitive, and economical alternative to the cumbersome stool collection methods that have previously been used for evaluation of water and sanitation projects.

We conducted a study to determine if use of a new flocculant-disinfectant home water treatment reduced diarrhea. We randomly assigned 492 rural Guatemalan households to five different water treatment groups: flocculant-disinfectant, flocculant-disinfectant plus a customized vessel, bleach, bleach plus a vessel, and control. During one year of observation, residents of control households had 4.31 episodes of diarrhea per 100 person-weeks, whereas the incidence of diarrhea was 24% lower among residents of households receiving flocculant-disinfectant, 29% lower among those receiving flocculant-disinfectant plus vessel, 25% lower among those receiving bleach, and 12% lower among households receiving bleach plus vessel. In unannounced evaluations of home drinking water, free chlorine was detected in samples from 27% of flocculant-disinfectant households, 35% of flocculant-disinfectant plus vessel households, 35% of bleach households, and 43% of bleach plus vessel households. In a setting where diarrhea was a leading cause of death, intermittent use of home water treatment with flocculant-disinfectant decreased the incidence of diarrhea.

We compared epidemiologic characteristics of Cryptosporidium and Cyclospora in surveillance data from outpatient departments in Guatemala. Routinely-submitted stool specimens were screened by microscopy. Age, sex, and symptom data were collected. Cyclospora was detected in 117 (2.1%) and Cryptosporidium in 67 (1.2%) of 5,520 specimens. The prevalence of Cyclospora peaked in the warmer months, while Cryptosporidium was most common in the rainy season. Both affected children more than adults, but Cryptosporidium affected children at a younger age than Cyclospora (median age 2 years versus 5 years; P < 0.001). Cyclospora showed a stronger association with diarrhea than Cryptosporidium, even when data were stratified by age. These contrasts may reflect differences in the relative importance of transmission modes, the frequency of exposure, and the development of immunity.

In 1996 and 1997, cyclosporiasis outbreaks in North America were linked to eating Guatemalan raspberries. We conducted a study in health-care facilities and among raspberry farm workers, as well as a case-control study, to assess risk factors for the disease in Guatemala. From April 6, 1997, to March 19, 1998, 126 (2.3%) of 5, 552 surveillance specimens tested positive for Cyclospora; prevalence peaked in June (6.7%). Infection was most common among children 1.5 to 9 years old and among persons with gastroenteritis. Among 182 raspberry farm workers and family members monitored from April 6 to May 29, six had Cyclospora infection. In the case-control analysis, 62 (91%) of 68 persons with Cyclospora infection reported drinking untreated water in the 2 weeks before illness, compared with 88 (73%) of 120 controls (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.4, 10.8 by univariate analysis). Other risk factors included water source, type of sewage drainage, ownership of chickens or other fowl, and contact with soil (among children younger than 2 years).

There is still controversy over the impact of diabetes control and duration on bone mass and growth parameters in children and adolescents with insulin-dependent diabetes mellitus (IDDM). The aim of this study was to assess bone mineral density (BMD) at axial and appendicular sites, in children with noncomplicated IDDM of recent onset, and its relation to metabolic control and auxological parameters (weight, height, and puberal stage). Fifty-five young Spanish IDDM, otherwise healthy patients (26 males, aged (SD 9.7 +/- 4.3 years) and 29 females, aged (SD 11.2 +/- 3.8 years) were studied. Duration of diabetes was 1-13.8 years. Two hundred eighty-two age-matched, healthy, Spanish children served as controls. HbA1 was assayed by high pressure liquid chromatography (HPLC) and BMD was measured using dual X-ray absorptiometry (DXA) densitometry at the spine and forearm. Results showed a Gaussian BMD distribution of patients according to sex and age, without sexual-stage differences. There was no correlation between BMD and glycated hemoglobin (average life disease or last HbA1 values) or duration of the disease; moreover, no differences in bone mass were found between <3 and >/=3 years of disease duration. Diabetes impact index (mean HbA1 x duration of disease in months) showed no significant influence of diabetes control on BMD. We could not demonstrate any impact of diabetes on BMD and growth parameters in children with IDDM of short duration.

Osteoporosis is a well-known side-effect of chronic treatment with glucocorticoids. We have studied vertebral bone mineral density (BMD) and biochemical markers of bone metabolism in 30 patients diagnosed of Addison's disease (AD) to determine the effect of long-term replacement treatment with hydrocortisone (30 mg/day) or prednisone (7.5 mg/day). Lumbar bone mineral density was measured with dual energy X-ray absorptiometry in L-1-4 in two occasions, separated by 12 months. BMD in premenopausal women and men with AD was similar to healthy controls and postmenopausal women had slightly lower results. Rate of change of bone density followed up over a period of 12 months was -0.82%. Bone loss was not influenced by duration or type of steroid treatment. Biochemical parameters, serum calcium, alkaline phosphatase, osteocalcin, procollagen type I, PTH and 25(OH)vitamin D were within normal limits. Our results show that in patients with AD, after replacement with low doses of glucocorticoids there is no significative trabecular bone loss neither modifications in bone formation markers.

We have studied bone turnover markers and bone mineral density (BMD) in 82 patients (26 females and 56 males) that underwent orthotopic liver transplantation in our center. Follow-up was for a median of 19.2 months (range 1-60 months). During this period they were treated with prednisone, azathioprine and cyclosporine in accordance with protocols. Spinal bone loss was measured with a dual energy X-ray densitometer (precision 1.3%), and, depending on Z score and BMD values, two groups were distinguished: A) Without osteoporosis: 47 patients, Z = -0.98 +/- 0.09 and BMD 0.899 +/- 0.098 g/cm2, and B) With osteoporosis: 35 patients, Z = -2.71 +/- 0.55 and BMD 0.739 +/- 0.080 g/cm2 (X +/- SD). Serum bone markers such as osteocalcin (BGP) 10.0 +/- 0.8 ng/ml and procollagen-I (pColl-I) 268.1 +/- 32.1 micrograms/ml, were found to be increased. Serum PTH was within the normal range. No significant differences were found between the etiologic subgroups studied with respect to bone loss. Also, no correlation was found between bone loss and duration of follow-up or other factors, such as immunosuppressant drugs or acute rejection. Our study confirms an increased prevalence of bone loss in patients with liver transplantation, which is associated with a high bone turnover, indicating that earlier diagnosis and treatment is necessary to improve survival and quality of life in these patients.

This study investigated the effect of long-term treatment upon bone density with L-Thyroxine in postmenopausal women compared with untreated postmenopausal women with climacteric symptoms. We measured spinal bone density in three groups (n = 84) of postmenopausal women: (A) those treated with TSH-suppressive doses of L-Thyroxine for a medium of 5 years after removal of thyroid cancer; (B) those on L-Thyroxine treatment for a median of 9 years after being diagnosed with chronic lymphocytic thyroiditis (CLT); and (C) those with no thyroid disease or other known pathology and without any treatment. There were no differences in dietary calcium intake and daily activity between untreated and L-Thyroxine-treated women. Measurements of bone mineral density were performed at spine level L1-L4 using a dual X-ray densitometer and serum thyroid-stimulating hormone (TSH), thyroid hormones, and bone markers (serum osteocalcin, procollagen I, urinary calcium), and PTH levels were assayed and found to be within normal ranges. Women receiving L-Thyroxine after thyroid cancer had slightly higher FT4 levels compared with women who had CLT and lower TSH levels, with serum T4 and T3 levels normal and similar in both groups. No significant differences were found in spinal bone density after L-Thyroxine treatment between Groups A and B and compared with Group C. Bone loss according to 2 SD below reference standards (age and sex matched) was found in the 12.9% of L-Thyroxine-treated patients versus 22.6% of untreated women. No correlation was found between bone loss and thyroid hormone levels and duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

We compared the incidence of heart failure (CHF), CHF mortality and CHF severity in cancer patients (pts) treated with doxorubicin (DXR) in the presence and absence of cardiologic monitoring (CM). CM consisted of endomyocardial biopsy and right heart catheterization as definitive tests with and without echocardiograms and phonocardiographically derived systolic time intervals as screening tests. CHF incidence was very low (0.03) in non-CM pts without risk factors (RF). RF pts had a CHF incidence of 0.17 without and 0.06 with CM (P = 0.107). Five of 58 RF pts in the non-CM group and 0 of 49 RF pts in the CM group died of problems related to CHF. CHF symptomatology by NYHA criteria was less in CM RF pts than non-CM RF pts (P = 0.034). The prevention of CHF mortality and morbidity in CM pts was not due to administering less DXR, as CM pts actually received an average of 43 mg/m2 more DXR than non-CM pts. We conclude that pts without RF need no CM during treatment with DXR, and that CM can reduce CHF severity and CHF mortality in RF pts.

A new, potent hypocholesterolemic agent is produced by cultures of Aspergillus terreus. The isolation of the compound and its characterization as 4a,5-dihydromevinolin containing a trans-fused octahydro-naphthalene system are described. Comparative data for dihydromevinolin and mevinolin in three biological assays are given: in vitro inhibition of HMG-CoA reductase, inhibition of sterol synthesis in cell cultures, and inhibition of cholesterol synthesis in vivo in rats.