Assessment of innovative living and care arrangements for persons with dementia: a systematic review.

BACKGROUND: Alternative forms of housing for persons with dementia have been developed in recent decades. These concepts offer small groups of residents familiar settings combined with efforts to provide normal daily life. The aim of this systematic review is to collate and analyze these more innovative forms of housing regarding residents' quality of life, behavioral aspects, as well as functional, cognitive and emotional aspects. METHODS: Searches were conducted in PubMed, EMBASE and PsycInfo in November 2020. Studies comparing traditional and more innovative living environments for persons with dementia were eligible. Concepts are described based on the results of additional searches. Risk of bias of included studies was assessed using checklists from the Joanna Briggs Institute. RESULTS: A total of 21 studies corresponding to 11 different concepts were included, namely Green Houses (USA), Group Living (Sweden), Cantou (France), Group Homes (Japan), Small-scale Group Living (Austria), Special Care Facilities (Canada), Shared-housing Arrangements (Germany), Residential Groups (Germany), Residential Care Centers / Woodside Places (USA/Canada), Small-scale Living (Netherlands/ Belgium), and Green Care Farms (Netherlands). The concepts are broadly similar in terms of care concepts, but partly differ in group sizes, staff qualifications and responsibilities. Several studies indicate that innovative forms of housing may encourage social behavior, preserve activity performance and/or positively influence emotional status compared to more traditional settings, while other studies fail to demonstrate these effects. Some studies also show increased behavioral and psychological symptoms of dementia (BPSD) in residents who live in more innovative housing concepts. The effect on cognition remains indistinct. DISCUSSION: The positive effects may be attributable to the inherent characteristics, including small group sizes, a stimulating design, and altered staff roles and responsibilities. Arguably, some of these characteristics might also be the reason for increased BPSD. Studies had variable methodological quality and results have to be considered with caution. Future research should examine these effects more closely and should investigate populations' preferences with regards to housing in the event of dementia.

Dominant GDAP1 mutations cause predominantly mild CMT phenotypes.

OBJECTIVE: Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT). We aimed to investigate the frequency of disease-causing heterozygous GDAP1 mutations in ADCMT and their associated phenotype. METHODS: We performed mutation analysis in a large cohort of ADCMT patients by means of bidirectional sequencing of coding regions and exon-intron boundaries of GDAP1. Intragenic GDAP1 deletions were excluded using an allele quantification assay. We confirmed the pathogenic character of one sequence variant by in vitro experiments assaying mitochondrial morphology and function. RESULTS: In 8 Charcot-Marie-Tooth disease (CMT) families we identified 4 pathogenic heterozygous GDAP1 mutations, 3 of which are novel. Three of the mutations displayed reduced disease penetrance. Disease onset in the affected individuals was variable, ranging from early childhood to adulthood. Disease progression was slow in most patients and overall severity milder than typically seen in autosomal recessive GDAP1 mutations. Electrophysiologic changes are heterogeneous but compatible with axonal neuropathy in the majority of patients. CONCLUSIONS: With this study, we broaden the phenotypic and genetic spectrum of autosomal dominant GDAP1-associated neuropathies. We show that patients with dominant GDAP1 mutations may display clear axonal CMT, but may also have only minimal clinical and electrophysiologic abnormalities. We demonstrate that cell-based functional assays can be reliably used to test the pathogenicity of unknown variants. We discuss the implications of phenotypic variability and the reduced penetrance of autosomal dominant GDAP1 mutations for CMT diagnostic testing and counseling.

Can sites prone to flow induced vascular complications in a-v fistulas be assessed using computational fluid dynamics?

Arterio-venous fistulas (shunts between arteries and veins) are the preferred vascular access for hemodialysis. Despite their superior patency, compared with synthetic tubes and grafts, functional problems and inadequate flow rates are the common complications. Local flow conditions, in particular low and oscillating wall shear stresses (WSS), are central to vascular problems and a robust framework for analyzing flow conditions in vascular structures could provide an understanding of the mechanisms leading to vascular complications, such as stenoses, aneurisms, and thromboses. We hypothesize that a validated computational fluid dynamics (CFD) framework can be used to identify critical fistula configurations with elevated risk of complications. Therefore, the aim of the present study was to develop a CFD framework for analyzing fluid flow in complex vascular structures, such as arterio-venous fistulas validated by comparisons of in vitro volume flows with CFD results and flow fields from ultrasound scans with CFD simulations. Volume flows measured in vitro and CFD data differed quantitatively. However, good relative correlations exist between the data using logarithmic scales. Qualitatively, visual comparisons between ultrasound and CFD images showed good agreement between the two methods. In addition, WSS levels and the oscillatory shear index (OSI) were calculated and visualized on the model surface. The method was successfully validated and the method is deemed suitable for more thorough investigations into the field of vascular complications in a-v fistulas.

Storm water management in an urban catchment: effects of source control and real-time management of sewer systems on receiving water quality.

For the examination of the effects of different storm water management strategies in an urban catchment area on receiving water quality, an integrated simulation of the sewer system, wastewater treatment plant and receiving water is carried out. In the sewer system real-time control measures are implemented. As examples of source control measures the reduction of wastewater and the reduction of the amount of impervious surfaces producing storm water discharges are examined. The surface runoff calculation and the simulation of the sewer system and the WWTP are based on a MATLAB/SIMULINK simulation environment. The impact of the measures on the receiving water is simulated using AQUASIM. It can be shown that the examined storm water management measures, especially the source control measures, can reduce the combined sewer overflow volume and the pollutant discharge load considerably. All examined measures also have positive effects on the receiving water quality. Moreover, the reduction of impervious surfaces avoids combined sewer overflow activities, and in consequence prevents pollutants from discharging into the receiving water after small rainfall events. However, the receiving water quality improvement may not be seen as important enough to avoid acute receiving water effects in general.

[Socioeconomic significance of dementia and mild cognitive disorders]. / Sozioökonomische Bedeutung der Demenz und leichter kognitiver Störungen.

While diagnostic criteria and epidemiologic results are available for dementia, reliable quantitative information on mild cognitive impairment is rare. The distinction between mild cognitive impairment, effects of normal ageing and dementia can be difficult to establish. Conceptual problems notwithstanding, a growing number of patients with dementia and with mild cognitive impairment can be safely predicted. Reduced quality of life on the part of patients and their families, growing demand for care and increasing costs of illness will prove the socioeconomic relevance of dementia.

Effects of real time control of sewer systems on treatment plant performance and receiving water quality.

Four individual mathematical submodels simulating different subsystems of urban drainage were intercoupled to an integral model. The submodels (for surface runoff, flow in sewer system, wastewater treatment plant and receiving water) were calibrated on the basis of field data measured in an existing urban catchment investigation. Three different strategies for controlling the discharge in the sewer network were defined and implemented in the integral model. The impact of these control measures was quantified by representative immission state-parameters of the receiving water. The results reveal that the effect of a control measure may be ambivalent, depending on the referred component of a complex drainage system. Furthermore, it is demonstrated that the drainage system in the catchment investigation can be considerably optimised towards environmental protection and operation efficiency if an appropriate real time control on the integral scale is applied.

Fluorescence properties and staining behavior of monodansylpentane, a structural homologue of the lysosomotropic agent monodansylcadaverine.

We have recently shown that monodansylcadaverine labels autophagic vacuoles. Analysis of the mechanism underlying the labeling revealed that monodansylcadaverine acts as a lysosomotropic agent, being concentrated into acidic compartments by an ion-trapping mechanism, and as a solvent polarity probe, increasing its relative fluorescence intensity by interacting with membrane lipids that are highly concentrated in the autophagic vacuoles. In this study, we synthesized three structurally related derivatives of monodansylcadaverine, replacing the primary amino group of monodansylcadaverine with a neutral (dansylamylamine; MDH), a polar (dansylaminopentanol; MDOH), or an acidic group (dansylaminovaleric acid; MDA), to replace the lysosomotropic character of the marker. Whereas MDH showed a specific staining of autophagic vacuoles, the polar and acidic derivatives did not show any staining. We further demonstrate that the MDH staining of autophagic vacuoles is independent on the acidic pH and thus on an ion-trapping mechanism, but it still shows the same preferences for autophagic membrane lipids as monodansylcadaverine. We propose that MDH can specifically interact with lamellar bodies of the autophagic type as a solvent polarity probe. Therefore, dansylated aminopentane can be used as a specific marker for autophagic vacuoles in vivo and in fixed cells.(J Histochem Cytochem 49:177-185, 2001)

The lysosomotropic agent monodansylcadaverine also acts as a solvent polarity probe.

The autofluorescent substance monodansylcadaverine has recently been reported as a specific in vivo marker for autophagic vacuoles. However, the mechanism for this specific labeling remained unclear. Our results reveal that the common model of ion trapping in acidic compartments cannot completely account for the observed autophagic vacuole staining. Because autophagic vacuoles are characterized by myelin-like membrane inclusions, we tested whether this lipid-rich environment is responsible for the staining properties of monodansylcadaverine. In in vitro experiments using either liposomes or solvents of different polarity, monodansylcadaverine showed an increased relative fluorescence intensity in a hydrophobic environment as well as a Stokes shift dependent on the solvent polarity. To test the effect of autophagic vacuoles or autophagic vacuole lipids on monodansylcadaverine fluorescence, we isolated autophagic vacuoles and purified autophagic vacuole lipids depleted of proteins. Entire autophagic vacuoles and autophagic vacuole lipids had the same effect on monodansylcadaverine fluorescence properties, suggesting lipids as the responsible component. Our results suggest that the in vivo fluorescence properties of monodansylcadaverine do not depend exclusively on accumulation in acidic compartments by ion trapping but also on an effective interaction of this molecule with autophagic vacuole membrane lipids. (J Histochem Cytochem 48:251-258, 2000)

CYFRA 8/18 in head and neck cancer.

BACKGROUND: Cytokeratins (Ck) 8, 18 and 19 that are normally expressed in head and neck tissue in only small amounts, become overexpressed in head and neck squamous cell cancerous tissue. It was questioned whether Ck 8 and 18, which occur together, were also detectable and of value as a tumor markers for this cancer entity. MATERIALS AND METHODS: One hundred forty-nine sera from patients with squamous cell carcinoma of the head and neck (SCCHN) were investigated with a novel ELISA kit for the detection of fragments of Ck 8 and 18. Twenty-five sera from healthy volunteers and 39 patients with benign diseases of the head and neck region served as controls. RESULTS: It was found that CYFRA 8/18 had a sensitivity of 7%. CYFRA 8/18 values did not show a correlation with clinical parameters. CONCLUSIONS: Because of a low sensitivity CYFRA 8/18 seems not to be of value as a tumor marker for SCCHN.

Relation between plasma tumor necrosis factor-alpha and insulin sensitivity in elderly men with non-insulin-dependent diabetes mellitus.

Human obesity is associated with an increased tumor necrosis factor-alpha (TNF-alpha) mRNA expression in adipose tissue. TNF-alpha decreases insulin-dependent glucose uptake by inhibiting autophosphorylation of the insulin receptor, suggesting that TNF-alpha may play a role in insulin resistance. In this study, we analyzed plasma levels of TNF-alpha in 40 70-year-old men with newly detected non-insulin-dependent diabetes mellitus and in 20 age-matched controls. Twenty of the patients had a moderate level of insulin resistance and 20 were severely insulin resistant. The plasma levels of TNF-alpha were higher in patients (4.00+/-1.53 pg/mL in moderately insulin resistant and 4.91+/-1.43 pg/mL in severely insulin resistant subjects) than in controls (3.27+/-0.79 pg/mL, P<0.001). TNF-alpha was significantly related to body mass index, fasting glucose levels, and serum triglyceride levels and inversely related to the high density lipoprotein cholesterol level. The finding of an association between high plasma levels of TNF-alpha and several metabolic abnormalities characteristic for the insulin resistance syndrome suggests that TNF-alpha may be involved in the pathogenesis of non-insulin-dependent diabetes mellitus.

Nodular amyloidosis of the tongue.

Amyloidosis is a rare disease in otorhinolaryngology. It presents a wide range of clinical manifestations and its deposits can be found in various organs. In the paper, a case of a 73-year-old female patient with macroglossia, as a symptom of nodular amyloidosis is reported. The predominant features were dysphagia and speech impairment caused by the tongue protruding beyond the teeth. The histologic appearance consisted of a nodular pattern of amyloid deposition. The amyloid was of an AL (lambda-light chain) type as shown immunohistochemically. The presented case shows the importance of investigating the patient for co-existing disease.

An animal model to study local oxidation of LDL and its biological effects in the arterial wall.

Oxidized LDL (oxLDL) is present in atherosclerotic lesions and is believed to play a key role in atherogenesis. Mainly on the basis of cell culture studies, oxLDL has been shown to produce many biological effects that influence the atherosclerotic process. To study LDL oxidation in vivo, we have established a model in which Sprague-Dawley rats are given a single injection of unmodified human LDL (> or = 4 mg/kg body weight). Within 6 hours, an accumulation of apolipoprotein B and epitopes present on oxLDL are detected in the arterial endothelium and media. The presence of oxLDL is associated with activation of the transcription factor nuclear factor-kappaB in the endothelium as well as endothelial expression of intercellular adhesion molecule-1. Injection of LDL enriched with the antioxidant probucol resulted in arterial accumulation of apolipoprotein B, but the expression of oxLDL-specific epitopes was reduced at 24 hours. Thus, this simple model has the potential to analyze the mechanisms behind and biological effects of LDL oxidation in vivo.

Differentially expressed genes in head and neck cancer.

Carcinogenesis is considered a multistep process. To further elucidate involved genetic changes, the differential display method was applied to compare gene expression of head and neck carcinoma cells and normal keratinocytes from the upper aerodigestive tract. Total RNA was extracted from cultured squamous carcinoma cells and keratinocytes. mRNA was reverse transcribed into cDNA, amplified by PCR, and separated on a gel. Currently three DNA transcripts were identified with a length of 191 to 336 base pairs (bp) that were either expressed only by the keratinocytes or by the malignant cells. Differentially expressed DNA fragments of the carcinoma cells and the keratinocytes were cloned and sequenced. A gene bank database search identified one fragment expressed by the carcinoma cells as an unknown gene, another one found in the keratinocytes as probably a part of the human cell attachment domain, and the third one with homology to the mRNA of the human epidermal growth factor receptor (EGFR). Northern blot analysis confirmed the differential expression in the malignant cells or the keratinocytes. Differential display seems to confirm the well-known overexpression and up-regulation of the EGFR, the differential expression of the cell attachment domain may play a role as a cofactor in carcinogenesis of head and neck cancer, and the third unknown fragment is still under investigation to elucidate the role in carcinogenesis.

[Primary mucous membrane melanoma of the base of the tongue]. / Primäres Schleimhautmelanom des Zungengrundes.

BACKGROUND: Primary mucosal melanoma of the tongue is an absolute rarity. A review of the literature revealed only 28 cases. PATIENT: The following report deals with an 87-year-old male patient who developed a primary melanoma of the left base of his tongue. The melanoma was excised with the CO2 laser. The patient refused surgical removal of the lymph nodes as well as radiation therapy. RESULTS: The laser resection of the melanoma led to a local control of the tumor at its primary site until the patient died from a stroke 30 months after the initial diagnosis. CONCLUSION: Limited melanoma of the mucosa of the tongue can be excised with the CO2 laser, if the resection can be performed with margins of healthy tissue as large as those in conventional surgery. Surgical therapy with primary palliative intention seems also to be adequate as relief of local symptoms can be achieved even for a longer period of time.

Human papillomaviruses in hypopharyngeal squamous cell carcinoma.

Human papillomaviruses (HPV) have been detected in squamous cell carcinoma (SCC) of the aerodigestive tract with varying frequency of 10%-100% mainly due to detection methods and primer pairs used. Polymerase chain reaction (PCR) is the most sensitive and Southern blot hybridization (SBH) the most specific detection method of HPV DNA. Both methods achieve the most reliable results. 22 SCC DNA samples of the hypopharynx were analyzed by type specific and consensus primer PCR and Southern blot analysis. HPV was detected in 5/22 (22.6%) hypopharyngeal SCC specimens. HPV 18 and HPV 45 were identified in one case each. An HPV prevalence of 23% is a realistic approximation in hypopharyngeal SCC. The high rate of HPV positive only detected by non type specific detection methods indicates the presence of previously undescribed HPV types.

Cut-off value determination of CYFRA 21-1 for squamous cell carcinomas of the head and neck (SCCHN).

BACKGROUND: CYFRA 21-1 was found to be a sensitive and specific tumor marker especially for squamous cell carcinomas of the lung. There is no reliable tumor marker for squamous cell carcinomas of the head and neck (SCCHN) available. METHODS: The amount of Cytokeratin (Ck) 19 in healthy tissue and tissues of benign and malignant tumors from pharynx, larynx and lung was compared utilizing a dot-blot assay. CYFRA 21-1 serum levels were determined prior to therapy in 132 healthy controls, in a reference group consisting of 158 patients with benign diseases of the head and neck and in 238 patients with a histologically proven SCCHN. RESULTS: Compared to lung tissue Ck 19 levels were similar only in specimen of SCCHN. Ck 19 content in normal and benign tissue from pharynx and larynx was lower than in normal lung tissue. CYFRA 21-1 serum levels were significantly higher in patients with SCCHN compared to the control or reference group. The cut-off value for CYFRA 21-1 determined at a 95%-specificity of the reference group was found to be 2.2 ng/ml. CONCLUSIONS: The Ck 19 level in healthy tissue of the upper aerodigestive tract was lower than in normal lung tissue. Corresponding to this finding the CYFRA 21-1 serum level in the reference group with benign diseases of the head and neck was lower than that of patients with benign lung diseases. The cut-off level of CYFRA 21-1 for patients with SCCHN was determined to be 2.2 ng/ml.

The soluble interleukin-2 receptor--a marker for squamous cell carcinoma of the upper aerodigestive tract.

Various studies indicate that the soluble interleukin-2 receptor (sIL-2R) is of value as marker in chronic and malignant disorders. No data are available on sIL-2R levels in head and neck cancer. The serum of 86 patients with squamous cell carcinoma of the head and neck (SCCHN) prior to any therapy and of 25 healthy controls was taken. Six month later the serum of 49 patients was taken again. sIL-2R levels were determined with ELISA. Patients with SCCHN prior to therapy had significantly elevated sIL-2R serum levels (895 U/ml) compared to controls (437 U/ml). After an eight month follow up 78.4% of the SCCHN patients with tumor recurrence had increased and 80% of the carcinoma patients without recurrence had decreased sIL-2R levels compared to prior to therapy. sIL-2R seems to be an unspecific marker for SCCHN and may be of prognostic value.

[Mucous membrane melanomas of the upper aerodigestive tract. An analysis of 34 cases]. / Schleimhautmelanome der oberen Luft- und Speisewege. Eine Analyse von 34 Fällen.

BACKGROUND: Malignant mucosal melanoma of the upper aerodigestive tract is a rare disease. The prognosis is expected to be significantly worse than the prognosis of cutaneous melanoma and so far no uniform therapeutic concept exists. Publications about mucosal melanoma are scarce and reported patient groups are usually small. PATIENTS: Thirty-four patients have been registered at the ENT Department of the University of Kiel Medical Center with the diagnosis mentioned above. Clinical data were obtained from the patient's charts, the minimum follow-up was three years. RESULTS: Most common site of the tumor was the nasal cavity and paranasal sinuses with 28 of 34 patients. Less frequently affected was the nasopharynx (three cases), oropharynx, larynx, and middle ear (one case each). All patients were caucasians and most of them were of an advanced age (66.9 years +/- 12.3). Treatment of choice was surgical resection in 27 cases, in four cases it was combined with radiation therapy, in one case with radiation therapy and chemotherapy, and in three cases with chemotherapy. Six patients received solely radiation therapy, one patient was only treated by chemotherapy. Patients who were treated by a combined approach had a more favourable outcome than patients who were treated by a monotherapy of surgery, radiation therapy, or chemotherapy. A high number of recurrences were observed, which occurred on an average of 16.6 months after the diagnosis of the primary tumor. Overall 5-year survival was 45.8%, the 10-year survival rate was 22.3%. CONCLUSIONS: Optimized combined therapeutical approaches might possibly improve the prognosis of mucosal melanoma of the upper aerodigestive tract. Intervals between follow-ups should be short to render detection of relapses at an early stage. Repeated therapy of recurrent disease might lengthen survival.

[Detection of differentially expressed genes in head-neck carcinomas]. / Untersuchungen zum Nachweis differentiell experimierter Gene bei Kopf-Hals-Karzinomen.

BACKGROUND: Carcinogenesis is generally considered a multistage process based on many alterations of the genetic substance. These alterations lead to many qualitative and quantitative changes in gene expression with subsequent malignant transformation of the cell. Only a few of these genetic alterations are identified yet. METHODS: The differential display reverse transcriptase polymerase chain reaction was employed to detect differentially expressed genes in head and neck cancer. The mRNA expression of cultivated keratinocytes of the upper aerodigestive tract was compared to the one of cultivated squamous cell carcinoma cells of the larynx, hypopharynx, and floor of the mouth. RESULTS: A total of 116 differentially expressed gene fragments were identified. They were either solely expressed by the malignant cells or the keratinocytes or in just one carcinoma cell entity. Forty-three of the 116 DNA fragments were sequenced successfully. In four cases the specific differential expression was confirmed by Northern blot hybridisation in comparison to keratinocytes, normal mucosa, and 3 benign tumors from the head and neck region. A gene bank search revealed in three cases a homology of less than 20% to already known human, animal, bacterial or viral gene sequences and in one case a homology of 98% with a human gene sequence. CONCLUSIONS: The detected for squamous cell carcinoma of the head and neck specific genes or gene fragments are the basis for further investigations to better understand carcinogenesis.

[Reproducibility of nonradioactive DDRT-PCR method for detection of gene expression in squamous epithelial carcinoma cells of the upper aerodigestive tract]. / Untersuchungen zur Reproduzierbarkeit einer nichtradioaktiven DDRT-PCR-Methode zum Nachweis der Genexpression in Plattenepithelkarzinomzellen der oberen Luft- und Speisewege.

BACKGROUND: The analysis of the gene spectrum in tumor and normal cells may provide information about genes involved in the differentiation or in the genesis of tumors. Differential Display Reverse Transcriptase Polymerase Chain Reaction (DDRT-PCR) is an innovative method that enables quick analysis of almost all mRNA molecules expressed in the cells. METHODS: In the trials, the mRNAs of keratinocytes and tumor cells were amplified by a number of oligonucleotide pairs after reverse transcription and resolved on polyacrylamide gel. A modified protocol for the amplification of cDNA probes was devised for detecting PCR products with silver nitrate. RESULTS: After reverse transcription of mRNAs, all cDNA samples were successfully amplified using the protocol devised for the silver nitrate DDRT-PCR, and the differentially expressed fragments were reproducibly demonstrated. CONCLUSIONS: The high reproducibility and feasibility of silver nitrate DDRT-PCR expand the alternatives for analyzing gene expression and detecting selectively expressed genes in different kinds of cells.