New, effective antibiotics are only likely to become available in 15 - 20 years. To prevent deaths from untreatable Gram-negative infections in South Africa, the rights of any doctor, whether in general or in hospital practice, to indiscriminately prescribe whatever antibiotic they wish, and in whatever fashion, must be challenged. Furthermore, although prevention of the emergence and subsequent spread of carbapenem-resistant Enterobacteriaceae (CRE) has focused on acute and chronic care facilities and inter alia on antibiotic exposure in these institutions, CRE may soon become an issue within entire communities, highlighting a role for public health authorities in CRE prevention efforts.
View Article and Find Full Text PDFSmall regulatory RNAs (sRNAs) are short, generally noncoding RNAs that act posttranscriptionally to control target gene expression. Over the past 10 years there has been a rapid expansion in the discovery and characterization of sRNAs in a diverse range of bacteria. Paradigm shifts in our understanding of the breadth of posttranscriptional control by sRNAs were achieved in a number of pioneering studies that involved immunoprecipitation of a known RNA chaperone, the near-ubiquitous Hfq, followed by sequencing to identify novel putative regulators and targets.
View Article and Find Full Text PDFBackground: Several observational studies have suggested a link between health status and rate of decline among individuals with Alzheimer's disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression.
Methods: This was a case-only cohort study arising from a population-based longitudinal study of memory and aging, in Cache County, Utah.
Background: Increased sensitivity and exposure to stress are associated with psychotic symptoms in schizophrenia and its risk states, but little is known about the co-evolution of stress sensitivity and exposure with positive and other symptoms in a clinical high-risk (CHR) cohort.
Method: A combined cross-sectional and longitudinal design was used to examine the associations over time of stress sensitivity and exposure (i.e.
Docetaxel is a taxane-derived chemotherapy drug that has been approved for treatment of prostate cancer. While docetaxel is frequently used as a treatment for hormone-refractory prostate cancer, a subset of patients either do not respond to this treatment or those that do respond eventually become resistant to the drug over time. Resistance to docetaxel is complex and multi-factoral and further understanding of the cellular biochemistry underlying resistance is vital to improve treatment efficacy.
View Article and Find Full Text PDFBackground: Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process.
Methods: We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls) and rectal (n = 754 cases, 959 controls) cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH), SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk.
Closer relationships between caregivers and care recipients with dementia are associated with positive outcomes for care recipients, but it is unclear if closeness is a risk or protective factor for the health and psychological wellbeing of caregivers. We examined 234 care dyads from the population-based Cache County Dementia Progression Study. Caregivers included spouses (49%) and adult offspring (51%).
View Article and Find Full Text PDFPro-oxidant and anti-oxidant genetic and lifestyle factors can contribute to an individual's level of oxidative stress. We hypothesize that diet, lifestyle and genetic factors work together to influence colon and rectal cancer through an oxidative balance mechanism. We evaluated nine markers for eosinophil peroxidase (EPX), two for myeloperoxidase (MPO), four for hypoxia-inducible factor-1A (HIFIA), and 16 for inducible nitric oxide synthase (NOS2A) in conjunction with dietary antioxidants, aspirin/NSAID use, and cigarette smoking.
View Article and Find Full Text PDFBalancing progenitor cell self-renewal and differentiation is essential for brain development and is regulated by the activity of chromatin remodeling complexes. Nevertheless, linking chromatin changes to specific pathways that control cortical histogenesis remains a challenge. Here we identify a genetic interaction between the chromatin remodeler Snf2l and Foxg1, a key regulator of neurogenesis.
View Article and Find Full Text PDFSocial challenges during the perinatal period influence the mother-infant relationship in nonhuman primates and may affect the offspring's response to later social challenge(s). Relocation of a breeding colony of monkeys (Macaca radiata) created two groups of infants: one group experienced social group relocation to a new housing facility during the perinatal period (ATYPICAL) and the second group developed within a constant environment (TYPICAL). At a mean age of 25 months, all animals were removed from their natal group and placed in same sex adolescent social groups.
View Article and Find Full Text PDFMicF is a textbook example of a small regulatory RNA (sRNA) that acts on a trans-encoded target mRNA through imperfect base pairing. Discovery of MicF as a post-transcriptional repressor of the major Escherichia coli porin OmpF established the paradigm for a meanwhile common mechanism of translational inhibition, through antisense sequestration of a ribosome binding site. However, whether MicF regulates additional genes has remained unknown for almost three decades.
View Article and Find Full Text PDFEarly Interv Psychiatry
February 2013
Aim: A biased attributional style, in which negative events are attributed to external and personal causes, is associated with paranoid delusions in schizophrenia. It is not known whether this biased attributional style also characterizes individuals at clinical risk for psychosis or if it is associated with their emergent paranoia.
Methods: Thirty-three clinical high-risk patients and 15 age- and gender-similar controls were assessed with the Internal, Personal, and Situational Attributions Questionnaire for externalizing and personalizing attributional biases and for potential correlates with suspiciousness and other symptoms.
Objective: The use of psychotropic medications in Alzheimer's disease (AD) has been associated with both deleterious and potentially beneficial outcomes. We examined the longitudinal association of psychotropic medication use with cognitive, functional, and neuropsychiatric symptom (NPS) trajectories among community-ascertained incident AD cases from the Cache County Dementia Progression Study.
Methods: A total of 230 participants were followed for a mean of 3.
Background: While increasing evidence suggests that cannabis use may play a role in the development of schizophrenia in some young people, less is known about the strength and specificity of its relationship to latent schizophrenia liability, i.e., schizotypal personality disorder traits.
View Article and Find Full Text PDFBackground: Observational studies suggest that cholinesterase inhibitors and/or memantine may delay clinical progression of Alzheimer's disease (AD) in 40% of individuals taking the medications. Given this response and existence of side effects, we sought to quantify medication use and benefits in a population-based study of incident AD cases.
Methods: The Cache County Dementia Progression Study enrolled and followed a cohort of 327 incident AD cases for a maximum of 9 years.
Background: Stress sensitivity and HPA axis activity may be relevant to the development and expression of psychotic disorders. Cortisol secretion has been associated with positive symptoms both in patients with psychotic disorders and in young people at clinical risk for psychosis. Herein, we aimed to replicate these findings, to determine which positive symptoms may be associated with cortisol levels, and to explore any associations with affective symptoms and impaired stress tolerance.
View Article and Find Full Text PDFBackground: Pneumocystis pneumonia (PCP) is a major cause of hospitalization and mortality in HIV-infected African children. Microbiologic diagnosis relies predominantly on silver or immunofluorescent staining of a lower respiratory tract (LRT) specimens which are difficult to obtain in children. Diagnosis on upper respiratory tract (URT) specimens using PCR has been reported useful in adults, but data in children are limited.
View Article and Find Full Text PDFAdverse early experiences are associated with a range of deleterious health outcomes in humans, including higher risk for affective disorders. Studies using a long-standing model of nonhuman primate model of early adversity have demonstrated that nursery-reared (NR) monkeys exhibit alterations in multiple aspects of biobehavioral development; however, few studies have evaluated the persistence of socioaffective behavioral changes through adulthood. We evaluated the effects of early rearing experience on adult animals' response to a well-validated assessment of anxiety-like behavior, the human intruder paradigm (HIP).
View Article and Find Full Text PDFBackground: There is no effective treatment strategy for advanced castration-resistant prostate cancer. Although Docetaxel (Taxotere®) represents the most active chemotherapeutic agent it only gives a modest survival advantage with most patients eventually progressing because of inherent or acquired drug resistance. The aims of this study were to further investigate the mechanisms of resistance to Docetaxel.
View Article and Find Full Text PDFExosomes are nano-sized, cell membrane surrounded structures that are released from many cell types. These exosomes are believed to transport a range of molecules, including mRNAs, miRNAs, and proteins; the contents depending on their cell of origin. The physiological and pathological relevance of exosomes has yet to be fully elucidated.
View Article and Find Full Text PDFObjectives: Early parental death is associated with lifelong tendencies toward depression and chronic stress. We tested the hypothesis that early parental death is associated with higher risk for Alzheimer disease (AD) in offspring.
Design: A population-based epidemiological study of dementia with detailed clinical evaluations, linked to one of the world's richest sources of objective genealogical and vital statistics data.
Background: Patients with schizophrenia have a decreased ability to interpret the intentions of other individuals, called Theory of Mind (ToM). As capacity for ToM normally advances with brain maturation, research on ToM in individuals at heightened clinical risk for psychosis may reveal developmental differences independent of disease based differences.
Methods: We examined ToM in at clinical high risk and schizophrenia patients as well as healthy controls: 1) 63 clinical high risk (CHR) patients and 24 normal youths ascertained by a CHR program; and 2) in 13 schizophrenia cases and 14 normal adults recruited through a schizophrenia program.
Objectives: Progression of Alzheimer dementia (AD) is highly variable. Most estimates derive from convenience samples from dementia clinics or research centers where there is substantial potential for survival bias and other distortions. In a population-based sample of incident AD cases, we examined progression of impairment in cognition, function, and neuropsychiatric symptoms, and the influence of selected variables on these domains.
View Article and Find Full Text PDF