Prevalence of stress, anxiety and depression in with Alzheimer caregivers

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease presents a social and public health problem affecting millions of Italians. Those affected receive home care from caregivers, subjected to risk of stress.</p> <p>The present investigation focuses on stress, anxiety and depression in caregivers.</p> <p>Methods</p> <p>Data on 200 caregivers and their patients were collected using a specific form to assess cognitive, behavioural, functional patient (MMSE, and ADL-IAD) and caregiver stress (CBI). The relationship between stress, depression and disease has been assessed by means of a linear regression, logistic analysis which reveals the relationship between anxiety, stress and depression and cognitive problems, age, the patient's income.</p> <p>Results</p> <p>The caregivers are usually female (64%), mean age of 56.1 years, daughters (70.5%), pensioners and housewives (30%), who care for the sick at home (79%). Of these, 53% had little time for themselves, 55% observed worsening of health, 56% are tired, 51% are not getting enough sleep. Overall, 55% have problems with the patient's family and/or their own family, 57% at work. Furthermore, 29% feel they are failing to cope with the situation as they wish to move away from home. The increase in the degree of anxiety and depression is directly proportional to the severity of the illness, affecting the patient (r = 0.3 stress and depression r = 0.4 related to CBI score). The memory disorders (OR = 8.4), engine problems (OR = 2.6), perception disorders (OR = 1.9) sick of the patient with Alzheimer's disease are predictive of caregiver stress, depression is associated with the presence of other disorders, mainly behavioural (OR = 5.2), low income (OR = 3.4), patients < 65 years of age (OR = 2.9).</p> <p>Conclusion</p> <p>The quality of life of caregivers is correlated with the severity of behavioural disorders and duration of the Alzheimer's disease. The severity of the disease plays an important role in reorganization of the family environment in families caring for patients not institutionalised. It is important to promote measures to soften the impact that the patient has on the caregiver, and that, at the same time, improves the quality of life of the patient.</p

Simplified low-cost production of O-antigen from Salmonella Typhimurium Generalized Modules for Membrane Antigens (GMMA)

AbstractThe Novartis Vaccines Institute for Global Health is developing vaccines using outer membrane particles, known as Generalized Modules for Membrane Antigens (GMMA). These are blebs of outer membrane and periplasm, shed from the surface of living Gram-negative bacteria following the targeted deletion of proteins involved in maintaining the integrity of the inner and outer membranes. The current study investigates the use of GMMA as starting material for extraction of membrane components, focusing on the O-antigen polysaccharide portion of lipopolysaccharide from Salmonella Typhimurium. We show that the amount of O-antigen extracted from GMMA by acid hydrolysis is comparable to the quantity extracted from whole wild type bacteria, but with less protein and DNA contaminants. Compared to conventional purification, GMMA enabled a reduction in the number of purification steps required to obtain the O-antigen polysaccharide with the same purity. Purification processes from GMMA and bacteria were characterised by similar final yields. Use of GMMA as starting material provides the possibility to simplify the purification process of O-antigen, with a consequent decrease in manufacturing costs of O-antigen-based glyconjugate vaccines against Salmonella strains and potentially other Gram-negative bacteria

Production of a Shigella sonnei Vaccine Based on Generalized Modules for Membrane Antigens (GMMA), 1790GAHB.

Recently, we developed a high yield production process for outer membrane particles from genetically modified bacteria, called Generalized Modules of Membrane Antigens (GMMA), and the corresponding simple two step filtration purification, enabling economic manufacture of these particles for use as vaccines. Using a Shigella sonnei strain that was genetically modified to produce penta-acylated lipopolysaccharide (LPS) with reduced endotoxicity and to maintain the virulence plasmid encoding for the immunodominant O antigen component of the LPS, scale up of the process to GMP pilot scale was straightforward and gave high yields of GMMA with required purity and consistent results. GMMA were formulated with Alhydrogel and were highly immunogenic in mice and rabbits. In mice, a single immunization containing 29 ng protein and 1.75 ng of O antigen elicited substantial anti-LPS antibody levels. As GMMA contain LPS and lipoproteins, assessing potential reactogenicity was a key aspect of vaccine development. In an in vitro monocyte activation test, GMMA from the production strain showed a 600-fold lower stimulatory activity than GMMA with unmodified LPS. Two in vivo tests confirmed the low potential for reactogenicity. We established a modified rabbit pyrogenicity test based on the European Pharmacopoeia pyrogens method but using intramuscular administration of the full human dose (100 μg of protein). The vaccine elicited an average temperature rise of 0.5°C within four hours after administration, which was considered acceptable and showed that the test is able to detect a pyrogenic response. Furthermore, a repeat dose toxicology study in rabbits using intramuscular (100 μg/dose), intranasal (80 μg/dose), and intradermal (10 μg/dose) administration routes showed good tolerability of the vaccine by all routes and supported its suitability for use in humans. The S. sonnei GMMA vaccine is now in Phase 1 dose-escalation clinical trials

Monocyte activation test of 1859-GMMA (red X) and reference (green •) and GMP batches of 1790-GMMA (blue +) measured by the IL-6 production from human PBMC.

<p>Each sample was measured in duplicate. The horizontal dashed line is the IL-6 level ten times background. At this level, 1790-GMMA required 600x times the concentration of 1859-GMMA to give the same level of IL-6 release.</p

Coomassie Blue stained SDS-PAGE of 1, 3 and 5 μg protein of 1790-GMMA from the reference batch.

<p>Coomassie Blue stained SDS-PAGE of 1, 3 and 5 μg protein of 1790-GMMA from the reference batch.</p

Transmission electron micrograph of purified 1790-GMMA from the GMP batch.

<p>The length of the bar in the micrographs is 200 nm.</p

Mass spectra of lipid A extracted from 1859-GMMA (top panel) and 1790-GMMA (lower panel).

<p>The peak with the biggest m/z from the 1859-GMMA sample is the size expected for a hexa-acylated lipid A. No hexa-acyl lipid A was detected in the 1790-GMMA. The peak with the highest <i>m/z</i> in the 1790-GMMA lipid A sample has the mass expected for penta-acylated lipid A consistent with the Δ<i>htrB</i> mutation</p

Mean temperature rise (mean of post vaccination–pre-vaccination temperature) in rabbits after an IM injection of 100 μg protein containing dose of 1790GAHB (red circles) or equivalent volume of physiological saline (blue diamonds).

<p>The vertical bars show the standard error of the mean. N = 12 for the 1790GAHB and 6 for the saline injected rabbits.</p