Health measurement instruments and their applicability to military veterans: a systematic review.

INTRODUCTION: Accurate measurement of health status is essential to assess veterans' needs and the effects of interventions directed at improving veterans' well-being. We conducted a systematic review to identify instruments that measure subjective health status, considering four components (ie, physical, mental, social or spiritual well-being). METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, JSTOR, ERIC, Social Sciences Abstracts and ProQuest in June 2021 for studies reporting on the development or evaluation of instruments measuring subjective health among outpatient populations. We assessed risk of bias with the Consensus-based Standards for the Selection of Health Measurement Instruments tool and engaged three veteran partners to independently assess the clarity and applicability of identified instruments. RESULTS: Of 5863 abstracts screened, we identified 45 eligible articles that reported health-related instruments in the following categories: general health (n=19), mental health (n=7), physical health (n=8), social health (n=3) and spiritual health (n=8). We found evidence for adequate internal consistency for 39 instruments (87%) and good test-retest reliability for 24 (53%) instruments. Of these, our veteran partners identified five instruments for the measurement of subjective health (Military to Civilian Questionnaire (M2C-Q), Veterans RAND 36-Item Health Survey (VR-36), Short Form 36, Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and Sleep Health Scale) as clear and very applicable to veterans. Of the two instruments developed and validated among veterans, the 16-item M2C-Q considered most components of health (mental, social and spiritual). Of the three instruments not validated among veterans, only the 26-item WHOQOL-BREF considered all four components of health. CONCLUSION: We identified 45 health measurement instruments of which, among those reporting adequate psychometric properties and endorsed by our veteran partners, 2 instruments showed the most promise for measurement of subjective health. The M2C-Q, which requires augmentation to capture physical health (eg, the physical component score of the VR-36), and the WHOQOL-BREF, which requires validation among veterans.

Phenotypic plasticity in plasmodial slime molds and molecular phylogeny of terrestrial vs. aquatic species.

Fifty years ago, the enigmatic Brazilian myxomycete-species Didymium aquatile was described and analyzed with respect to the structure of the plasmodium and its spores. In this study, we compare this rare plasmodial slime mold with another, temporarily aquatic taxon from Europe, Didymium nigripes. Phenotypic plasticity of D. nigripes was investigated under various environmental conditions. Large changes in the morphology of the plasmodia were observed. For species identification, characteristics of the fruiting bodies are key features. However, Didymium aquatile was only characterized by its "abnormal" plasmodia, but no molecular data were available. Here, we analyzed DNA-sequences of 22 species of the genera Didymium and Diderma with a focus on this South American taxon via molecular genetics. A comparison of 18S-rDNA-sequences from D. aquatile and 21 other Didymium (and Diderma)-species indicates that D. aquatile is a reproductively isolated morpho-species. Phenotypic plasticity of D. nigripes is documented with respect to plasmodium morphology and the formation of fruiting bodies, as an example of an adaptation of a terrestrial species to aquatic environments.

Stimulation with Porphyromonas gingivalis enhances malignancy and initiates anoikis resistance in immortalized oral keratinocytes.

The aim of this study was to get new insights into molecular processes involved in tumor propagation of immortalized oral keratinocytes induced by the keystone pathogen Porphyromonas gingivalis. Cell culture experiments with immortalized OKF6 cells were performed to analyze cellular effects caused by bacterial stimulation focusing on altered gene expression, signaling pathways, proliferation rate, cell viability, migration and invasion behavior, and on the development of antiapoptotic pathways. Gene and protein expression were analyzed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, western blot, and protein arrays. Trypan blue staining was used to analyze proliferation and viability, transwell assays for cellular migration, Matrigel assays for invasion, and anoikis-assays for evaluating anoikis resistance. Stimulation of OKF6 cells with Porphyromonas gingivalis led to an alteration in the molecular repertoire of proteins which are involved in cell proliferation, epithelial-mesenchymal transition, stem cell formation, migration, invasion, and anoikis resistance. Higher proliferation rates were detected in conjunction with an activation of PI3K/Akt signaling and the mTOR-pathway. Additionally, inhibition of glycogen-synthase-kinase3-ß led to stabilization of ß-catenin and Snail, which resulted in a switch from predominant E-cadherin to N-cadherin expression and increased expression of the stem cell markers Oct3/4, Sox2, and Nanog. Enhanced biosynthesis and enzyme activity of matrix metalloproteinase-9 was accompanied by elevated invasion behavior. Finally, anoikis resistance was detected in stimulated keratinocytes by decreased apoptosis of nonadherent cells and elevated expression of epidermal growth factor receptor and c-Met. Hence, Porphyromonas gingivalis is able to induce a more aggressive tumor-like phenotype in immortalized oral keratinocytes, thus contributing to enhanced tumor features.

Response of MG63 osteoblasts on bacterial challenge is dependent on the state of differentiation.

The present in vitro study examines molecular processes that are relevant during bone homeostasis after Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis infection with a focus on the differentiation level of osteoblasts. Regenerative processes are often hindered by the recurrence of bacterial infections, which can ultimately provoke a severe destruction of bone tissue. To obtain more detailed insights into such a complex scenario, we have used undifferentiated MG63 osteoblast-like cells as an experimental paradigm to examine the impact of two oral pathogens, A. actinomycetemcomitans and P. gingivalis, on proliferation, cytotoxicity and osteogenic differentiation. Cell culture experiments were performed to analyze cellular behavior. The level of genes interfering with bone tissue integrity (matrix metalloproteinases and their tissue inhibitors) and osteogenic markers (alkaline phosphatase, Runx2, human ß-defensin-2) was compared in undifferentiated versus differentiated MG63 cells using real-time polymerase chain reaction. Functional activity of matrix metalloproteinases was quantified by zymography. Western blot analysis was used to verify the phosphorylation state of mitogen-activated protein kinases p38 and extracellular-signal-regulated kinases 1/2. When co-cultured with undifferentiated MG63 cells, oral pathogens provoked distinct cellular effects. Only A. actinomycetemcomitans reduced cell proliferation, increased cell death, and induced osteogenic differentiation. A comparison of matrix metalloproteinase network stability in the presence of oral pathogens revealed a partial sensitivity towards P. gingivalis but not A. actinomycetemcomitans. So, beside the proof of concept that MG63 cells co-cultured with oral pathogens can serve as an in vitro model for mimicking destructive and regenerative events after bacterial infections, our data indicate that double infections might counterbalance otherwise positive effects.

Oral pathogens change proliferation properties of oral tumor cells by affecting gene expression of human defensins.

The impact of oral pathogens onto the generation and variability of oral tumors has only recently been investigated. To get further insights, oral cancer cells were treated with pathogens and additionally, as a result of this bacterial cellular infection, with human defensins, which are as anti-microbial peptide members of the innate immune system. After cell stimulation, proliferation behavior, expression analysis of oncogenic relevant defensin genes, and effects on EGFR signaling were investigated. The expression of oncogenic relevant anti-microbial peptides was analyzed with real-time PCR and immunohistochemistry. Cell culture experiments were performed to examine cellular impacts caused by stimulation, i.e., altered gene expression, proliferation rate, and EGF receptor-dependent signaling. Incubation of oral tumor cells with an oral pathogen (Porphyromonas gingivalis) and human α-defensins led to an increase in cell proliferation. In contrast, another oral bacterium used, Aggregatibacter actinomycetemcomitans, enhanced cell death. The bacteria and anti-microbial peptides exhibited diverse effects on the transcript levels of oncogenic relevant defensin genes and epidermal growth factor receptor signaling. These two oral pathogens exhibited opposite primary effects on the proliferation behavior of oral tumor cells. Nevertheless, both microbe species led to similar secondary impacts on the proliferation rate by modifying expression levels of oncogenic relevant α-defensin genes. In this respect, oral pathogens exerted multiplying effects on tumor cell proliferation. Additionally, human defensins were shown to differently influence epidermal growth factor receptor signaling, supporting the hypothesis that these anti-microbial peptides serve as ligands of EGFR, thus modifying the proliferation behavior of oral tumor cells.

Moisturizing treatment of patients with atopic dermatitis and ichthyosis vulgaris improves dry skin, but has a modest effect on gene expression regardless of FLG genotype.

BACKGROUND: Loss-of-function mutations in FLG (encoding filaggrin) are a predisposing factor for atopic dermatitis (AD) and cause ichthyosis vulgaris (IV). Patients with AD and IV display impaired skin barrier and dry skin, and altered epidermal expression of genes in pro-inflammatory and lipid metabolic pathways are often evident. OBJECTIVES: To evaluate the effect of three different moisturizers on skin barrier function and epidermal gene expression in patients with AD/IV in relation to FLG mutation status. METHODS: Patients (n = 43) were classified according to their FLG status: AD with FLG+/+ (n = 14), AD with FLG+/- (n = 14), and AD/IV with FLG-/- (n = 15). Dryness score and transepidermal water loss (TEWL) were monitored on volar forearms, and punch biopsies were taken for analysis of gene expression. Measurements were repeated after 4 weeks of treatment with either of two moisturizers on each forearm. RESULTS: Treatment with any of the three moisturizers significantly reduced dryness score and TEWL in the group as a whole. FLG-/- patients displayed the largest reduction in dryness score. Only minute changes occurred in the mRNA expression of 15 selected epidermal genes. CONCLUSIONS: Moisturizing treatment improves dry skin and certain aspects of abnormal skin barrier function, especially in patients with AD/IV and dual FLG mutations, but does not normalize the epidermal gene expression profile.

X-linked recessive ichthyosis: an impaired barrier function evokes limited gene responses before and after moisturizing treatments.

BACKGROUND: X-linked recessive ichthyosis (XLRI) is due to deletions or inactivating mutations in the steroid sulfatase (STS) gene. This results in an accumulation of cholesterol sulphate affecting the packing of intercorneocyte lipids. XLRI is characterized by dry, scaly skin and increased skin barrier permeability; patients are often dependent on daily use of moisturizers. OBJECTIVES: To examine the biophysical and molecular changes in the skin of patients with XLRI compared with healthy volunteers, and to analyse the effects of moisturizers on the patients' barrier function. METHODS: Patients with XLRI (n=14) and healthy controls (n=14) were included in the study. Skin dryness score, transepidermal water loss (TEWL) and skin surface pH were monitored at baseline, and punch biopsies were obtained for mRNA expression profiles determined by oligonucleotide arrays. Measurements were repeated in the patients with XLRI after a 4-week treatment with three different moisturizers on the volar forearms. RESULTS: Patients with XLRI showed, compared with healthy controls, increased dryness and TEWL, equal skin pH and altered expression of 27 genes. There were no signs of activation of inflammation or repair pathways. Five selected genes were significantly altered also on quantitative polymerase chain reaction analysis. Treatment with the moisturizers showed similar effects: they improved skin dryness but had no effect on TEWL, pH or expression of selected genes. CONCLUSIONS: Despite a dysfunctional skin barrier, the limited number of genes altered in XLRI skin suggests that no inflammatory or repair mechanisms are triggered. Treatment with moisturizers does not have any major impact on the skin barrier properties of patients with XLRI.

Low thymic size in preterm infants in the neonatal intensive care unit, a possible marker of infection? A prospective study from birth to 1 year of age.

AIM: To study the growth of the thymus in preterm infants. METHODS: Ultrasonographic thymic size (Ti) was studied in 80 preterm infants (gestational age 24-36 weeks) from birth to discharge from the neonatal intensive care unit (NICU). Thirty-three of these infants were followed to 1 year of age. RESULTS: At birth, the median Ti was 5.2 compared with 11.8 in term infants. At discharge, the median Ti was 10.0 and not significantly different from Ti in term infants at birth (p = 0.22). The size of the thymus was significantly associated with postmenstrual age and weight (both p < 0.01). Infections during admission were negatively associated with the size of the thymus (p < 0.01). During the first 3 months after discharge, preterm infants had a significantly higher frequency of infections than did term infants (p = 0.002); hereafter, the preterm infants had significantly fewer infections than term infants (p = 0.002). The median Ti in preterm infants and term infants at 1 year of age was 21.1 and 17.3, respectively. This difference was not statistically significant (p = 0.41). CONCLUSIONS: Growth of thymus was not compromised by preterm birth. Ti is negatively associated with the frequency of infections in preterm neonates submitted to NICU.

[Eligibility requirements after refractive surgery. Pilots, professional drivers and applicants for the police and armed forces]. / Tauglichkeitsanforderungen nach refraktivchirurgischen Eingriffen. Piloten, Berufskraftfahrer und Bewerber bei Polizei und Bundeswehr.

Selection of the appropriate refractive procedure is made by the surgeon according to medical criteria. However, some professions in the Federal Republic of Germany require certain eyesight standards and only permit the performance of certain refractive procedures. Therefore it is crucial for the surgeon to know whether a chosen refractive procedure and visual function meet the eligibility requirements of the patients' profession before the refractive procedure is carried out.The following article provides an overview of the current visual requirements after refractive surgery for pilots, professional drivers and applicants for the armed forces and the police force in the Federal Republic of Germany.

In the shadow of Darwin: Anton de Bary's origin of myxomycetology and a molecular phylogeny of the plasmodial slime molds.

In his Origin of Species (John Murray, London, 1859), Charles Darwin described the theory of descent with modification by means of natural selection and postulated that all life may have evolved from one or a few simple kinds of organisms. However, Darwin's concept of evolutionary change is entirely based on observations of populations of animals and plants. He briefly mentioned 'lower algae', but ignored amoebae, bacteria and other micro-organisms. In 1859, Anton de Bary, the founder of mycology and plant pathology, published a seminal paper on the biology and taxonomy of the plasmodial slime molds (myxomycetes). These heterotrophic protists are known primarily as a large composite mass, the plasmodium, in which single nuclei are suspended in a common 'naked' cytoplasm that is surrounded by a plasma membrane. Here we summarize the contents of de Bary's 1859 publication and highlight the significance of this scientific classic with respect to the establishment of the kingdom Protoctista (protists such as amoebae), the development of the protoplasmic theory of the cell, the introduction of the concept of symbiosis and the rejection of the dogma of spontaneous generation. We describe the life cycle of the myxomycetes, present new observations on the myxamoebae and propose a higher-order phylogeny based on elongation factor-1 alpha gene sequences. Our results document the congruence between the morphology-based taxonomy of the myxomycetes and molecular data. In addition, we show that free-living amoebae, common protists in the soil, are among the closest living relatives of the myxomycetes and conclude that de Bary's 'Amoeba-hypothesis' on the evolutionary origin of the plasmodial slime molds may have been correct.

[Modular semiquantitative quality assessment of ophthalmic health information on the internet--reproducibility and correlation between different assessment categories]. / Modulare semiquantitative Qualitätsbewertung augenheilkundlicher Gesundheitsinformationen im Internet--Reproduzierbarkeit und Korrelation zwischen verschiedenen Bewertungskategorien.

BACKGROUND: Quality evaluation of web-based health information in ophthalmology requires valid standards and reproducible assessment procedures. The objective was to evaluate the interrater-reliability of quality assessment of ophthalmic websites and a possible correlation between the results of the evaluation categories reliability/trustworthiness, quality of medical content and accessibility/usability. MATERIALS AND METHOD: After selection with the search engine "Google" 20 ophthalmic websites had been analysed by two independent evaluators using criteria checklists (modified Afgis transparency criteria, modified BITV test, medical content related to AMD) related to the aforementioned 3 categories. RESULTS: The interrater-reliability was almost perfectly estimated with Kappa-values of 0.91 for reliability/trustworthiness plus 0.89 for accessibility/usability and 0.79 for content. On average 62.5 % (+/- 17.43 %), 27.36 % (+/- 16.5 %) and 59.54 % (+/- 15.73 %) of the quality requirements were fulfilled for reliability/trustworthiness, content and accessibility/usability, respectively. No significant correlation was found between reliability and content (r = -0.039, p = 0.8709), reliability and accessibility/usability (r = -0.284; p = 0.228) plus content and accessibility/usability (r = 0.199; p = 0.4047). CONCLUSION: Sufficiently operationalised criteria are prerequisites for reproducible results of quality assessment of ophthalmic websites between different observers. The assessment within a single category, such as reliability/trustworthiness, does not allow one to draw conclusions on other categories such as content or accessibility/usability or the overall quality of a website. Therefore, simplified tools for quality assessment of health information by laymen and patients may have a limited validity.

[Accessibility of information on eye diseases on the internet for the visually impaired user]. / Zugänglichkeit von Informationsangeboten über Augenerkrankungen im Internet für sehbehinderte Nutzer.

BACKGROUND: The number of visually impaired people who use the internet for obtaining health information around the eye, is rising continuously. For this reason the accessibility for visually impaired persons to such websites is an important factor. Our investigation deals with the question: How good is the accessibility for the visually impaired to gather information on eye diseases on the Internet and how could this be improved? MATERIALS AND METHOD: After identification using the the search engine "Google", 20 websites of German university eye hospitals have been checked for their accessibility using the modified BITV test which is based upon 52 test criteria. RESULTS: On average 70.75 % (+/- 6.19 % min. 56.6 %, max; 86.79 %) of the required accessibility criteria have been fulfilled. This corresponds to an average accessibility value of 70.58 % (+/- 6.69 % min. 56.31 %, max. 89.32 %). According to the BITV test, this means that the average of the analysed websites is not accessible. The improper use of mark-up languages, unclear document or web page titles or missing alternative texts for pictures, graphics and navigation elements and misleading navigational architecture are frequent findings. This builds up the greatest accessibility barriers, although these barriers could be eliminated even with a relatively low expense. CONCLUSION: Good accessibility allows not only a barrier-free access to information for visually impaired users but is also a most important feature related to search engine optimisation.

Quantification of Enterobacteriaceae in faeces of captive black rhinoceros (Diceros bicornis) in relation to dietary tannin supplementation.

Free-ranging browsing herbivores ingest a range of secondary plant compounds, such as tannins, with their natural diet. As many of these substances have been shown to have antibacterial properties, it could be speculated that a lack of such compounds in captive zoo diets could favour the growth of potentially pathogenic intestinal bacteria. The effect of a supplementation of a conventional diet (N, consisting mainly of grass hay and/or lucerne hay and pelleted compound feeds) fed to eight captive black rhinoceroses (Diceros bicornis) from three zoological institutions with either tannic acid (T), a source of hydrolysable tannins, or quebracho (Q), a source of condensed tannins, was investigated. The number of faecal colony forming units (CFU) of Enterobactericeae was determined by colony count of dilution series from fresh faeces applied to MacConkey agar plates. Tannins were added to the diets at approximately 5-15 g/kg dry matter, depending on the varying intake of roughage and compound feeds by the animals. There was no difference in the number of CFU between diets N (95.0 x 10(5) +/- 225.3 x 10(5)/g fresh faeces) and T (164.3 x 10(5) +/- 225.1 x 10(5)/g fresh faeces); in contrast, diet Q led to a significant reduction in CFU (4.3 x 10(5) +/- 6.5 x 10(5)/g fresh faeces) compared with the other diets. These findings suggest that condensed tannins could have the potential to reduce the number of potentially pathogenic intestinal bacteria, and that the deliberate inclusion of tannin sources in the diets of captive wild animals should be further investigated. The fact that tannic acid, shown to have antibacterial effects in various in vitro studies, did not have an effect in this study, emphasizes that the relevance of tannin supplementation for intestinal health must be verified in vivo.

Less is more: how protein degradation regulates muscle development.

The organization of sarcomeric structures during muscle development involves regulated multistep assembly pathways. The myosin assembly factor UNC-45 functions both as a molecular chaperone and as an Hsp90 co-chaperone for myosin throughout muscle thick-filament formation. Consequently, mutations in unc-45 result in paralyzed worms with severe myofibril disorganization in striated body wall muscles. Our data suggest that functional muscle formation in Caenorhabditis elegans is linked to ubiquitin-dependent UNC-45 turnover, regulated by the E3 enzymes UFD-2 and CHN-1 in cooperation with the ubiquitin-selective chaperone CDC-48 (also known as p97 in human). Missense mutations in the gene encoding p97 are known to cause a dominant, late-onset hereditary inclusion body myopathy. Remarkably, we identified a conserved role of CDC-48/p97 in the process of myofiber differentiation and maintenance, which appears to have important implications for understanding defects in muscle formation and maintenance during pathological conditions.

[Bilateral anterior panuveitis as early manifestation of syphilis in a patient with HIV infection]. / Beidseitige Panuveitis als okuläre Frühmanifestation einer Lues bei einem Patienten mit HIV-1-Infektion.

INTRODUCTION: Syphilis is a dangerous sexually transmitted infection which can be effectively treated with penicillin to avoid late-onset diseases. Even if syphilis is diagnosed an HIV infection should be excluded. PATIENT: A 32-year-old homosexual man complained about a decreased bilateral visual acuity after a feverish infection with lymphadenitis colli. With slit-lamp biomicroscopy a bilateral panuveitis with papillary edema, endothelial cells and episcleritis was found. After antimycotic and antiviral therapy, his visual acuity decreased and symptoms progressed. In the lab routine we found lues and HIV infections and started an intravenous penicillin therapy immediately. A few days later the symptoms improved and visual acuity increased. CONCLUSION: Lues serology should be incorporated into routine lab diagnostics to aid the detection and to start the right therapy as soon as possible.

[Comments on the standards for acceptance and consistency testing of systems for digital radiography]. / Kommentierungen zu den Normen zu Abnahme- und Konstanzprüfungen bei digitalen Radiographiesystemen (Projektionsradiographie).

Due to German regulations, acceptance and consistency tests have to be obtained by 12.31.2005 for all equipment used for computed radiography according to special standards published in DIN 6868. This article familiarizes all users with the most important aspects of these standards. In addition, explanatory and background information for establishing these regulations are provided.

Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone.

The OLE pathway of yeast regulates the level of the ER-bound enzyme Delta9-fatty acid desaturase OLE1, thereby controlling membrane fluidity. A central component of this regulon is the transcription factor SPT23, a homolog of mammalian NF-kappaB. SPT23 is synthesized as an inactive, ER membrane-anchored precursor that is activated by regulated ubiquitin/proteasome-dependent processing (RUP). We now show that SPT23 dimerizes prior to processing and that the processed molecule, p90, retains its ubiquitin modification and initially remains tethered to its unprocessed, membrane-bound SPT23 partner. Subsequently, p90 is liberated from its partner for nuclear targeting by the activity of the chaperone-like CDC48(UFD1/NPL4) complex. Remarkably, this enzyme binds preferentially ubiquitinated substrates, suggesting that CDC48(UFD1/NPL4) is qualified to selectively remove ubiquitin conjugates from protein complexes.

Membrane-bound transcription factors: regulated release by RIP or RUP.

Regulated nuclear transport of transcription factors from cytoplasmic pools is a major route by which eukaryotes control gene expression. Exquisite examples are transcription factors that are kept in a dormant state in the cytosol by membrane anchors; such proteins are released from membranes by proteolytic cleavage, which enables these transcription factors to enter the nucleus. Cleavage can be mediated either by regulated intramembrane proteolysis (RIP) catalysed by specific membrane-bound proteases or by regulated ubiquitin/proteasome-dependent processing (RUP). In both cases processing can be controlled by cues that originate at or in the vicinity of the membrane.

Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing.

Processing of integral membrane proteins in order to liberate active proteins is of exquisite cellular importance. Examples are the processing events that govern sterol regulation, Notch signaling, the unfolded protein response, and APP fragmentation linked to Alzheimer's disease. In these cases, the proteins are thought to be processed by regulated intramembrane proteolysis, involving site-specific, membrane-localized proteases. Here we show that two homologous yeast transcription factors SPT23 and MGA2 are made as dormant ER/nuclear membrane-localized precursors and become activated by a completely different mechanism that involves ubiquitin/proteasome-dependent processing. SPT23 and MGA2 are relatives of mammalian NF-kappaB and control unsaturated fatty acid levels. Intriguingly, proteasome-dependent processing of SPT23 is regulated by fatty acid pools, suggesting that the precursor itself or interacting partners are sensors of membrane composition or fluidity.