An overview of co-morbidities and the development of pressure ulcers among older adults.

BACKGROUND: The prevalence of pressure ulcers particularly in the frail older adult population continues to be high and very costly especially in those suffering from chronic diseases and has brought a higher awareness to comprehensive, preventive and therapeutic measures for treatment of pressure ulcers. Internal risk factors highlighted by comorbidities play a crucial role in the pathogenesis of pressure ulcers. MAIN BODY: Focusing on the impact of common chronic diseases (comorbidities) in aging on pressure ulcers (e.g., cardiovascular diseases, diabetes, chronic pulmonary diseases, renal diseases and neurodegenerative disorders) and the significant complicating conditions e.g., anemia, infectious diseases, malnutrition, hospitalization, incontinence and polypharmacy, frailty and disability becomes important in developing a more complete, inclusive and multidisciplinary approach to prevention of PU in older patients. OBJECTIVE: To describe chronic and acute conditions which are risk factors in elderly patients for developing PU. METHODS: We present an overview of comorbidities seen with PU in three diverse patient locations. The inclusion criteria are sites (community, acute hospital and long term facilities), older patients, chronic diseases and pressure ulcers grade 2 and over. Using a recently developed conceptual framework accepted by European and National Pressure Ulcer Advisory Panels, we examined chronic diseases to identify the risk factors of chronic conditions and complicating conditions which potentially influence risk for PU development. CONCLUSION: Multiple chronic diseases and complicating factors which associated with immobility, tissue ischemia, and undernutrition are caused to PU in community settings, hospitals, and nursing facilities.

[Self endangerment to save life--competing Jewish legal and moral obligations].

The obligation to help others often involves personal risk. Consequently, the scope and boundaries of this obligation can present a complex dilemma, which has practical and moral implications, even in the world of medicine. In Jewish medical ethics, the dilemma stems from a confrontation between the duty to help others according to the biblical commandment: "Do not stand idly by your fellow's blood" on the one hand, and between the right and duty of man to defend himself, which is anchored in Jewish law. This article surveys the sources of this quandary in Jewish texts throughout the ages such as the Bible, Mishnah, Talmud, and responsa literature in various contexts. The discussion highlights the essential difference between the formal demands of the law, which protects human rights of self-preservation, and the moral requirement to help others even if it may include personal risk. The sources suggest distinguishing between various levels of risk ranging from high-risk to reasonable or low risk. In this way, the classic sources, provide the foundation and the tools for grappling with modern contemporary Halachic questions such as organ transplantation, and generate a Torah value-based framework to deal with new situations that may arise in the future. It is critical to assess the level of risk and the chances for success, along with other subjective considerations, in order to ensure the optimal ethical course of action.

[Truth telling to patients--A discussion of Jewish sources (corrected)].

Defining truth and truth-telling to patients are central topics in philosophy, law, and psychology, with many implications in medicine. In the last hundred years, with the transition from paternalistic medicine to a system in which the patient's autonomy is emphasized, the decision on the quantity and quality of medical information to be disclosed to the patient has become more complicated and requires careful consideration and special sensitivity on the part of the doctor. The Israeli Patients' Rights Act (1996] established guidelines for medical staff about telltting the truth to patients with occasional special authority delegated to the doctor to decide for the benefit of the patient at his discretion and with the approval of the institutional ethics committee, but in practice there are difficulties in implementing the Law. This article reviews a selection of sources from Jewish tradition throughout the ages that deal with truthtelling or concealing the truth in medical contexts and other contexts. Sources are drawn from the Bible, Mishna-Talmud, and halachic Literature, from which.conclusions can be drawn regarding this issue. In our opinion, these sources yield messages and values that are also relevant to the modern medical world. This is especially true in a multi-cultural environment such as Israel that requires the physician to consider the patient's background and to communicate information in accordance with his/her will, in an efficient and sensitive manner.

Immunological and autoimmune considerations of Autism Spectrum Disorders.

Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental conditions presenting in early childhood with a prevalence ranging from 0.7% to 2.64%. Social interaction and communication skills are impaired and children often present with unusual repetitive behavior. The condition persists for life with major implications for the individual, the family and the entire health care system. While the etiology of ASD remains unknown, various clues suggest a possible association with altered immune responses and ASD. Inflammation in the brain and CNS has been reported by several groups with notable microglia activation and increased cytokine production in postmortem brain specimens of young and old individuals with ASD. Moreover several laboratories have isolated distinctive brain and CNS reactive antibodies from individuals with ASD. Large population based epidemiological studies have established a correlation between ASD and a family history of autoimmune diseases, associations with MHC complex haplotypes, and abnormal levels of various inflammatory cytokines and immunological markers in the blood. In addition, there is evidence that antibodies that are only present in some mothers of children with ASD bind to fetal brain proteins and may be a marker or risk factor for ASD. Studies involving the injection of these ASD specific maternal serum antibodies into pregnant mice during gestation, or gestational exposure of Rhesus monkeys to IgG subclass of these antibodies, have consistently elicited behavioral changes in offspring that have relevance to ASD. We will summarize the various types of studies associating ASD with the immune system, critically evaluate the quality of these studies, and attempt to integrate them in a way that clarifies the areas of immune and autoimmune phenomena in ASD research that will be important indicators for future research.

A Retrospective Study of the Impact of Pressure Ulcers on Survival in Elderly Persons With Chronic Diseases.

Medical advancements are extending the lives of persons with chronic diseases, increasing their risk for pressure ulcer (PU) development. A retrospective chart review of 192 patients (49.48% male, mean age 9.7 ± 10.9 years) admitted to a skilled nursing department between 2008 and 2013 was performed to determine whether PUs and comorbidities, singly and combined, affect patient survival. Characteristics abstracted and assessed included sociodemographic factors (age, gender), diseases/comorbidities (eg, chronic renal failure, dementia, Parkinson's disease [PD], ischemic heart disease, and diabetes mellitus), persistent vegetative state (PVS), type and quantity of PUs (excluding Stage I and PUs that developed during the study), body mass index (BMI) <22, and laboratory data (serum albumin, total protein level, and hemoglobin [Hg] <10). Results were expressed as proportion or mean ± standard deviation. All statistical tests were 2-sided. A P value <.05 was considered significant. Hazard ratios (HR) and statistical significance for survival by risk factors were calculated by the Cox proportional hazards model. Univariate survival models were fitted for all risk factors. Statistical and clinical considerations were used to choose a subset of significant factors to include in a multivariate survival model; all chosen factors were fitted at the first step of the univariate survival models. Age, gender, and BMI were included in the model due to their known clinical effects on survival and their influence on other prognostic factors. In assessing anemia and Hg, only anemia was included due to multicollinearity. From the chosen factors fitted at the first step, a backward elimination was used to successively remove nonsignificant factors until all factors were significant at the 0.10 level. Patients were followed from hospitalization date until death or censoring of study. Median survival time was 122 days (CI: 82-192 days). The median survival time of patients with PUs was 72 days. Every increase in the number of PUs increased mortality by 14% (P <.001, HR = 1.14, CI: 1.07-1.20). In univariate analysis, PUs, anemia, dementia, and PD were found to have a significant association with decreased survival (P = .0001, .003, .001, and .004, respectively). In multivariate analysis, significant risk factors for decreasing survival time were the presence of PUs (HR = 1.14, P = .0001) and dementia (HR = 1.585, P = .009). Anemia (HR = 1.345, P = .09) and PVS (HR = 0.51, P = .09) were determined not to be significant. Anemia was found to decrease survival time and PVS was found to increase survival time. When number of PUs was combined with anemia, advanced dementia, or BMI, the median survival decreased from 72 days to 52, 63, and 63 days, respectively. These findings suggest that PUs in this population are not an isolated health problem but are 1 indicator of systemic deterioration and decreased survival time. The significance of knowing the survival time of patients with PUs has clinical and ethical implications for the comprehensive treatment of elderly patients, particularly those with advanced dementia and other associated medical conditions.

Monitoring the Efficacy of Oncolytic Viruses via Gene Expression.

With the recent success of oncolytic viruses in clinical trials, efforts toward improved monitoring of the viruses and their mechanism have intensified. Four main gene expression strategies have been employed to date including: analyzing overall gene expression in tumor cells, looking at gene expression of a few specific genes in the tumor cells, focusing on gene expression of specific transgenes introduced into the virus, and following gene expression of certain viral genes. Each strategy presents certain advantages and disadvantages over the others. Various methods to organize the dysregulated genes into clusters have provided a window into the mechanism of action for these viruses. Methodologically, the combined approach of looking at both overall gene expression, the tumor cells and gene expression of viral genes, enables researchers to assess correlation between the introduction of the virus and the changes in the tumor. This would seem to be the most productive approach for future studies, providing much information on mechanism and timing.

Variation in Gene Expression in Autism Spectrum Disorders: An Extensive Review of Transcriptomic Studies.

Autism spectrum disorders (ASDs) are a group of complex neurodevelopmental conditions that present in early childhood and have a current estimated prevalence of about 1 in 68 US children, 1 in 42 boys. ASDs are heterogeneous, and arise from epigenetic, genetic and environmental origins, yet, the exact etiology of ASDs still remains unknown. Individuals with ASDs are characterized by having deficits in social interaction, impaired communication and a range of stereotyped and repetitive behaviors. Currently, a diagnosis of ASD is based solely on behavioral assessments and phenotype. Hundreds of diverse ASD susceptibility genes have been identified, yet none of the mutations found account for more than a small subset of autism cases. Therefore, a genetic diagnosis is not yet possible for the majority of the ASD population. The susceptibility genes that have been identified are involved in a wide and varied range of biological functions. Since the genetics of ASDs is so diverse, information on genome function as provided by transcriptomic data is essential to further our understanding. Gene expression studies have been extremely useful in comparing groups of individuals with ASD and control samples in order to measure which genes (or group of genes) are dysregulated in the ASD group. Transcriptomic studies are essential as a key link between measuring protein levels and analyzing genetic information. This review of recent autism gene expression studies highlights genes that are expressed in the brain, immune system, and processes such as cell metabolism and embryology. Various biological processes have been shown to be implicated with ASD individuals as well as differences in gene expression levels between different types of biological tissues. Some studies use gene expression to attempt to separate autism into different subtypes. An updated list of genes shown to be significantly dysregulated in individuals with autism from all recent ASD expression studies will help further research isolate any patterns useful for diagnosis or understanding the mechanisms involved. The functional relevance of transcriptomic studies as a method of classifying and diagnosing ASD cannot be underestimated despite the possible limitations of transcriptomic studies.

Therapeutic properties of mesenchymal stem cells for autism spectrum disorders.

Recent studies of autism spectrum disorders (ASD) highlight hyperactivity of the immune system, irregular neuronal growth and increased size and number of microglia. Though the small sample size in many of these studies limits extrapolation to all individuals with ASD, there is mounting evidence of both immune and nervous system related pathogenesis in at least a subset of patients with ASD. Given the disturbing rise in incidence rates for ASD, and the fact that no pharmacological therapy for ASD has been approved by the Food and Drug Administration (FDA), there is an urgent need for new therapeutic options. Research in the therapeutic effects of mesenchymal stem cells (MSC) for other immunological and neurological conditions has shown promising results in preclinical and even clinical studies. MSC have demonstrated the ability to suppress the immune system and to promote neurogenesis with a promising safety profile. The working hypothesis of this paper is that the potentially synergistic ability of MSC to modulate a hyperactive immune system and its ability to promote neurogenesis make it an attractive potential therapeutic option specifically for ASD. Theoretical mechanisms of action will be suggested, but further research is necessary to support these hypothetical pathways. The choice of tissue source, type of cell, and most appropriate ages for therapeutic intervention remain open questions for further consideration. Concern over poor regulatory control of stem cell studies or treatment, and the unique ethical challenges that each child with ASD presents, demands that future research be conducted with particular caution before widespread use of the proposed therapeutic intervention is implemented.