Astroglial alterations in rat hippocampus during chronic lead exposure.

The present study was performed in order to follow the response of astroglial cells in the rat hippocampus to chronic low-level lead exposure. The experiments combined immunohistochemistry using anti-glial fibrillary acidic protein (GFAP) antibody and conventional transmission electron microscopy (EM). Chronic administration with drinking water [1 g% w/v (subclinical dose) of lead acetate dissolved in distilled water] was started through the mother's milk when pups were 7 days old. Following weaning, experimental offspring were treated for 3 months with the same concentration of adulterated water. The group of intoxicated animals and their controls were sacrificed by perfusion-fixation at 30, 60, and 90 days of exposure. After 60 days of lead treatment, staining of GFAP-positive cells demonstrated an astroglial transformation from the quiescent to the reactive state, characterized by an increase in GFAP. In control rats no changes in GFAP immunostaining were observed. The intensity of the astroglial response was enhanced after 90 days of lead intoxication, showing an increment of GFAP immunoreactivity. Quantification of these changes was made by computerized image analysis, confirming that the sectional areas of the astroglia in lead-exposed animals were larger than those in controls. These results are consistent with the ultrastructural alterations. Simultaneously with the increment in gliofilaments, intranuclear inclusions were seen in some astrocytes. The mechanisms by which lead affects astrocytes are unknown. Probably the astroglial changes induced by lead intoxication produce microenvironmental modifications that may disturb the neuronal function.     

Bacteremias in liver transplant recipients: shift toward gram-negative bacteria as predominant pathogens.

During the 1990s, gram-positive bacteria emerged as major pathogens after liver transplantation. We sought to determine whether the pathogens associated with bacteremias in liver transplant recipients have changed. Patients included 233 liver transplant recipients transplanted between 1989 and 2003. The proportion of all infections due to bacteremias increased significantly over time (P <.0001). Of other major infections, a trend toward a decrease in fungal infections (P =.089) and a significant decrease in cytomegalovirus (CMV) disease (P =.0004) were documented. Whereas the proportion of bacteremias due to gram-negatives increased from 25% in the period of 1989-1993 to 51.8% in 1998-03, that of gram-positive bacteria decreased from 75% in the period of 1989-93 to 48.2% in the period of 1998-2003. Methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent pathogens in bacteremic patients. The incidence of bacteremias due to MRSA and Pseudomonas aeruginosa has remained unchanged (P <.20); however, that due to enteric gram-negative bacteria, particularly Klebsiella pneumoniae has increased (P =.02). Klebsiella pneumoniae isolates in the current quartile were not clonally related. In conclusion, bacteremias as a proportion of all infections in liver transplant recipients have increased significantly over time, due in part to a decline in infections due to other major pathogens, e.g., fungi, primarily Candida species, and CMV. Gram-negative bacteria have emerged as predominant pathogens in bacteremic liver transplant recipients.     

Clinical and genetic characteristics of Stargardt disease in a large Western China cohort: Report 1

Stargardt disease 1 (STGD1) is the most prevalent retinal dystrophy caused by pathogenic biallelic ABCA4 variants. Forty‐two unrelated patients mostly originating from Western China were recruited. Comprehensive ophthalmological examinations, including visual acuity measurements (subjective function), fundus autofluorescence (retinal imaging), and full‐field electroretinography (objective function), were performed. Next‐generation sequencing (target/whole exome) and direct sequencing were conducted. Genotype grouping was performed based on the presence of deleterious variants. The median age of onset/age was 10.0 (5–52)/29.5 (12–72) years, and the median visual acuity in the right/left eye was 1.30 (0.15–2.28)/1.30 (0.15–2.28) in the logarithm of the minimum angle of resolution unit. Ten patients (10/38, 27.0%) showed confined macular dysfunction, and 27 (27/37, 73.7%) had generalized retinal dysfunction. Fifty‐eight pathogenic/likely pathogenic ABCA4 variants, including 14 novel variants, were identified. Eight patients (8/35, 22.8%) harbored multiple deleterious variants, and 17 (17/35, 48.6%) had a single deleterious variant. Significant associations were revealed between subjective functional, retinal imaging, and objective functional groups, identifying a significant genotype–phenotype association. This study illustrates a large phenotypic/genotypic spectrum in a large well‐characterized STGD1 cohort. A distinct genetic background of the Chinese population from the Caucasian population was identified; meanwhile, a genotype–phenotype association was similarly represented.     

Stainable hepatic iron in 341 African American adults at coroner/medical examiner autopsy

Background  

Results of previous autopsy studies indicate that increased hepatic iron stores or hepatic iron overload is common in African Americans dying in hospitals, but there are no reports of hepatic iron content in other cohorts of African Americans.     

Early introduction of allergenic foods for the prevention of food allergy from an Asian perspective—An Asia Pacific Association of Pediatric Allergy,Respirology & Immunology (APAPARI) consensus statement

Emerging evidence for the early introduction of allergenic foods for the prevention of food allergies, such as peanut allergy in Western populations, has led to the recent publication of guidelines in the USA and Europe recommending early peanut introduction for high‐risk infants with severe eczema or egg allergy. Peanut allergy is, however, much less prevalent in Asia compared to the West. Varying patterns of food allergy are seen even within Asian countries—such as a predominance of wheat allergy in Japan and Thailand and shellfish allergy in Singapore and the Philippines. Customs and traditions, such as diet and infant feeding practices, also differ between Asian populations. Hence, there are unique challenges in adapting guidelines on early allergenic food introduction to the Asian setting. In this paper, we review the evidence and discuss the possible approaches to guide the timely introduction of allergenic food in high‐risk infants in Asia.     

Ethyl glucuronide and ethyl sulfate: a review of their roles in forensic toxicology analysis of alcohol postmortem

Forensic Toxicology - This review presents the current methods used for determining ethyl glucuronide (EtG) and ethyl sulfate (EtS) concentrations in postmortem specimens, including sample...     

Intestinal Microbiota Containing Barnesiella Species Cures Vancomycin-Resistant Enterococcus faecium Colonization

Bacteria causing infections in hospitalized patients are increasingly antibiotic resistant. Classical infection control practices are only partially effective at preventing spread of antibiotic-resistant bacteria within hospitals. Because the density of intestinal colonization by the highly antibiotic-resistant bacterium vancomycin-resistant Enterococcus (VRE) can exceed 10⁹ organisms per gram of feces, even optimally implemented hygiene protocols often fail. Decreasing the density of intestinal colonization, therefore, represents an important approach to limit VRE transmission. We demonstrate that reintroduction of a diverse intestinal microbiota to densely VRE-colonized mice eliminates VRE from the intestinal tract. While oxygen-tolerant members of the microbiota are ineffective at eliminating VRE, administration of obligate anaerobic commensal bacteria to mice results in a billionfold reduction in the density of intestinal VRE colonization. 16S rRNA gene sequence analysis of intestinal bacterial populations isolated from mice that cleared VRE following microbiota reconstitution revealed that recolonization with a microbiota that contains Barnesiella correlates with VRE elimination. Characterization of the fecal microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation demonstrated that intestinal colonization with Barnesiella confers resistance to intestinal domination and bloodstream infection with VRE. Our studies indicate that obligate anaerobic bacteria belonging to the Barnesiella genus enable clearance of intestinal VRE colonization and may provide novel approaches to prevent the spread of highly antibiotic-resistant bacteria.     

Epidemiology and potential risk factors of drug-related problems in Hong Kong paediatric wards

Aims

A drug-related problem (DRP) is ‘an event or circumstance involving drug therapy that actually or potentially interferes with the desired health outcome’. The extent and characteristics of DRPs in children in Hong Kong are unknown. The aim of this study was to determine the epidemiology of and identify risk factors for DRPs in hospitalized children in Hong Kong.

Methods

This was a prospective cohort study in children aged 0–18 years who were admitted to a medical ward, paediatric intensive care unit or neonatal intensive care unit of seven Hong Kong hospitals, during a 3 month period. Patients'' charts, medical records and laboratory data were reviewed daily to identify DRPs; their preventability and severity were assessed. Logistic regression was used to analyse potential risk factors associated with the incidence of DRPs.

Results

Three hundred and twenty-nine children (median age, 2 years; interquartile range, 0 months to 9 years) were included. In total, 82 DRPs were experienced by 69 patients. The overall incidence of DRPs was 21.0% (95% confidence interval, 16.7–25.8%). The incidence was higher in neonatal and paediatric intensive care units than medical wards. Dosing problems were the most frequently reported DRPs (n = 35; 42.7%), followed by drug choice problems (n = 19; 23.2%) and adverse drug reactions (n = 11; 13.4%). Sixty-seven (81.7%) DRP cases were assessed as preventable, 42 (51.2%) as minor and 40 (48.8%) as moderate. The number of prescribed drugs and ‘certain infectious and parasitic diseases’ were potential risk factors for occurrence of DRPs.

Conclusions

Drug-related problems were common in hospitalized children in this study in Hong Kong; the most frequent were dosing and drug choice problems, and the majority of them were preventable. Polypharmacy and ‘certain infectious and parasitic diseases’ were potential risk factors.