Performance in a Balance Test and Prediction of All-Cause Mortality in Community-Dwelling Elderly Ambulatory Individuals: A Systematic Review and Meta-analysis.

Objective: This systematic review and meta-analysis was performed to evaluate the association between an inability to perform a static balance test and mortality in community-dwelling older ambulatory individuals. Methods: PubMed, Embase, and Scopus were searched for relevant cohort studies. Hazard ratios (HR) were pooled (random-effect model). Meta-regression was performed with independent demographic variables (PROSPERO ID: CRD42022381137). Results: A total of 11,713 articles were screened and 15 were included. An inability to perform a static balance test was significantly associated with a higher risk of mortality irrespective of whether confounding variables were considered [HR, 1.14 (95% CI: 1.07-1.21); p < .001; i2, 87.96% (p < .01)] or not [HR, 1.11 (95% CI: 1.03-1.20); p = .01; i2, 95.28% (p < .01)] (both moderate GRADE evidence). Also, this association was correlated with progressive age. Conclusion: An inability to successfully complete a static balance test was significantly associated with a higher risk of mortality among community-dwelling older ambulatory individuals.

In vitro quantification: Long-term effect of glucose deprivation on various cancer cell lines.

OBJECTIVE: Although metabolic treatment of highly glycolytic cancers and metastases is becoming an important research field, the effects of such treatments are not fully quantified yet. In this article we attempt to quantify the effect of long-term glucose deprivation (similar to ketogenic diets) on cancer cells using in vitro tests. METHODS: Two tumorigenic cell lines were used, namely a metastatic breast and a cervical cancer cell line. The non-tumorigenic control cell line was an immortalized breast cell line. All the cell lines were stabilized at a typical average human blood glucose level of 6 mmol/L. The cell lines were then exposed to the therapeutic blood glucose level of 3 mmol/L for 90 d. RESULTS: The tests indicated that glucose deprivation restricted the different cancer cell lines' growth more than that of non-tumorigenic cells. The different cell lines were also differentially affected, which suggests that long-term glucose deprivation will not be equally effective for different types of cancer. The highly glycolytic breast cancer cell line was most adversely affected, with cell growth decreasing to 30% after 26 d. Cell growth was stable at this level for up to 22 d. Furthermore, all of the other cancer cell lines were similarly affected. CONCLUSIONS: This in vitro data could help to direct future human in vivo tests to find the most therapeutic time (cancer cells at their most vulnerable) for additional short-term adjuvant therapies. Partial recovery of proliferation occurred after 90 d. Therefore, as expected, the results also indicated that without an adjuvant treatment, full extinction cannot be reached with the proposed long-term metabolic treatment. The need for more clinical data on long-term glucose deprivation treatments for cancer is well described in the literature. This paper attempts to add to the available pool of knowledge.

A hypothetical method for controlling highly glycolytic cancers and metastases.

Most proliferating cancer cells and cancer-associated tumor stroma have an upregulated glucose energy demand in relation to normal cells. Cancer cells are further less metabolically flexible than normal cells. They can therefore not survive metabolic stress as well as normal cells can. Metabolic deprivation thus provides a potential therapeutic window. Unfortunately, current glucose blockers have toxicity problems. An alternative way to reduce a cancer patient's blood glucose (BG), for a short-term period to very low levels, without the concomitant toxicity, is hypothesized in this paper. In vitro tests have shown that short-term BG deprivation to 2 mmol/L for 180 min is an effective cancer treatment. This level of hypoglycaemia can be maintained in vivo with a combination of very low-dose insulin and the suppression of the glucose counter-regulation system. Such suppression can be safely achieved by the infusion of somatostatin and a combination of both α and ß-blockers. The proposed short-term in vivo method, was shown to be non-toxic and safe for non-cancer patients. The next step is to test the effect of the proposed method on cancer patients. It is also suggested to incorporate well-known, long-term BG deprivation treatments to achieve maximum effect.

The integrated effect of moderate exercise on coronary heart disease.

BACKGROUND: Moderate exercise is associated with a lower risk for coronary heart disease (CHD). A suitable integrated model of the CHD pathogenetic pathways relevant to moderate exercise may help to elucidate this association. Such a model is currently not available in the literature. METHODS: An integrated model of CHD was developed and used to investigate pathogenetic pathways of importance between exercise and CHD. Using biomarker relative-risk data, the pathogenetic effects are representable as measurable effects based on changes in biomarkers. RESULTS: The integrated model provides insight into higherorder interactions underlying the associations between CHD and moderate exercise. A novel 'connection graph' was developed, which simplifies these interactions. It quantitatively illustrates the relationship between moderate exercise and various serological biomarkers of CHD. The connection graph of moderate exercise elucidates all the possible integrated actions through which risk reduction may occur. CONCLUSION: An integrated model of CHD provides a summary of the effects of moderate exercise on CHD. It also shows the importance of each CHD pathway that moderate exercise influences. The CHD risk-reducing effects of exercise appear to be primarily driven by decreased inflammation and altered metabolism.

Oral health and coronary heart disease.

BACKGROUND: It is well documented that there is some correlation between poor oral health in the form of periodontal disease and coronary heart disease (CHD). It is unclear whether this correlation is due to a causal relationship or shared underlying disorder such as inflammation. A suitable integrated model of the CHD pathogenetic pathways relevant to periodontal disease may help to elucidate the association. Such a model is currently not available in literature. METHODS: A previously developed integrated model of CHD was used to investigate potential pathogenetic pathways linking periodontal disease to CHD biomarkers. RESULTS: The integrated model was created to provide insight into possible higher-order biological interactions underlying CHD and periodontal disease. In order to simplify these interactions a novel 'connection graph' was developed. It quantitatively illustrates the relationship between periodontal disease and various serological biomarkers of CHD. The pathogenesis of periodontitis shows various possible pathways which could link periodontitis to CHD pathogenesis. CONCLUSION: An integrated model of CHD was developed which provides a summary of the potential CHD effects of periodontal disease. Further research must refine and validate the model.

Influence of Alluvial Morphology on Upscaled Hydraulic Conductivity.

The hydraulic conductivity of aquifers is a key parameter controlling the interactions between resource exploitation activities, such as unconventional gas production and natural groundwater systems. Furthermore, this parameter is often poorly constrained by typical data used for regional groundwater modeling and calibration studies performed as part of impact assessments. In this study, a systematic investigation is performed to understand the correspondence between the lithological descriptions of channel-type formation and the bulk effective hydraulic conductivities at a larger scale (Kxeff , Kyeff , and Kzeff in the direction of channel cross section, along the channel and in the vertical directions, respectively). This will inform decisions on what additional data gathering and modeling of the geological system can be performed to allow the critical bulk properties to be more accurately predicted. The systems studied are conceptualized as stacked meandering channels formed in an alluvial plain, and are represented as two facies. Such systems are often studied using very detailed numerical models. The main factors that may influence Kxeff , Kyeff , and Kzeff are the proportion of the facies representing connected channels, the aspect ratio of the channels, and the difference in hydraulic conductivity between facies. Our results show that in most cases, Kzeff is only weakly dependent on the orientations of channelized structures, with the main effects coming from channel aspect ratio and facies proportion.

Influence of partial and complete glutamine-and glucose deprivation of breast-and cervical tumorigenic cell lines.

BACKGROUND: Due to their high proliferative requirements, tumorigenic cells possess altered metabolic systems whereby cells utilize higher quantities of glutamine and glucose. These altered metabolic requirements make it of interest to investigate the effects of physiological non-tumorigenic concentrations of glucose and glutamine on tumorigenic cells since deprivation of either results in a canonical amino acid response in mammalian cell. METHODS: The influence of short-term exposure of tumorigenic cells to correlating decreasing glutamine- and glucose quantities were demonstrated in a highly glycolytic metastatic breast cell line and a cervical carcinoma cell line. Thereafter, cells were propagated in medium containing typical physiological concentrations of 1 mM glutamine and 6 mM glucose for 7 days. The effects on morphology were investigated by means of polarization-optical transmitted light differential interference contrast. Flow cytometry was used to demonstrate the effects of glutamine-and glucose starvation on cell cycle progression and apoptosis induction. Fluorometrics were also conducted to investigate the effects on intrinsic apoptosis induction (mitocapture), reactive oxygen species production (2,7-dichlorofluorescein diacetate) and acidic vesicle formation (acridine orange). RESULTS: Morphological data suggests that glutamine-and glucose deprivation resulted in reduced cell density and rounded cells. Glutamine-and glucose starvation also resulted in an increase in the G2M phase and a sub-G1 peak. Complete starvation of glutamine and glucose resulted in the reduction of the mitochondrial membrane potential in both cell lines with MDA-MB-231 cells more prominently affected when compared to HeLa cells. Further, starved cells could not be rescued sufficiently by propagating since cells possessed an increase in reactive oxygen species, acidic compartments and vacuole formation. CONCLUSION: Starvation from glutamine and glucose for short periods resulted in decreased cell density, rounded cells and apoptosis induction by means of reactive oxygen species generation and mitochondrial dysfunction. In addition, the metastatic cell line reacted more prominently to glutamine-and glucose starvation due to their highly glycolytic nature. Satisfactory cellular rescue was not possible as cells demonstrated oxidative stress and depolarized mitochondrial membrane potential. This study contributes to the knowledge regarding the in vitro effects and signal transduction of glucose and/or l-glutamine deprivation in tumorigenic cell lines.