Summary
Recent studies found that hepatitis C virus (HCV) may invade the central nervous system, and both HCV and Parkinson's disease (PD) have in common the overexpression of inflammatory ...biomarkers. We analysed data from a community‐based integrated screening programme based on a total of 62 276 subjects. We used logistic regression models to investigate association between HCV infection and PD. The neurotoxicity of HCV was evaluated in the midbrain neuron–glia coculture system in rats. The cytokine/chemokine array was performed to measure the differences of amounts of cytokines released from midbrain in the presence and absence of HCV. The crude odds ratios (ORs) for having PD were 0.62 95% confidence interval (CI), 0.48–0.81 and 1.91 (95% CI, 1.48–2.47) for hepatitis B virus (HBV) and HCV. After controlling for potential confounders, the association between HCV and PD remained statistically significant (adjusted OR = 1.39; 95% CI, 1.07–1.80), but not significantly different between HBV and PD. The HCV induced 60% dopaminergic neuron death in the midbrain neuron–glia coculture system in rats, similar to that of 1‐methyl‐4‐phenylpyridinium (MPP+) but not caused by HBV. This link was further supported by the finding that HCV infection may release the inflammatory cytokines, which may play a role in the pathogenesis of PD. In conclusion, our study demonstrated a significantly positive epidemiological association between HCV infection and PD and corroborated the dopaminergic toxicity of HCV similar to that of MPP+.
The efficacy of opioids typically decreases after long-term use owing to the development of tolerance. Glial activation and the upregulation of proinflammatory cytokines are related to the induction ...of tolerance. We investigated the effect of leukemia inhibitory factor (LIF) on morphine analgesia and tolerance.
LIF concentrations in rat spinal cords were measured by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) after morphine administration. LIF distribution was examined using confocal microscopy. To evaluate the effects of LIF on morphine analgesia and tolerance, LIF was intrathecally administered 30 min before morphine injection. The analgesic effect of morphine was evaluated by measuring tail-flick latency. Human LIF concentrations from the cerebrospinal fluid (CSF) of opioid tolerant patients were also determined by specific ELISA.
Chronic morphine administration upregulated LIF concentrations in rat spinal cords. Intrathecal injection of LIF potentiated the analgesic action of morphine. Patch clamp recording of spinal cord slices showed that LIF enhanced DAMGO (D-Ala2, N-MePhe4, Gly-ol-enkephalin)-induced outward potassium current. The development of tolerance was markedly suppressed by exogenous LIF, whereas neutralizing the endogenously released LIF with anti-LIF antibodies accelerated the tolerance induction. Moreover, LIF concentrations in the CSF of opioid-tolerant patients were higher than those in the opioid-naive controls.
Intrathecal administration of LIF potentiated morphine antinociceptive activity and attenuated the development of morphine tolerance. Upregulation of endogenously released LIF by long-term use of opioids might counterbalance the tolerance induction effects of other proinflammatory cytokines. LIF might be a novel drug candidate for inhibiting opioid tolerance induction.
Background and purpose
Earlier studies suggested an association between idiopathic restless legs syndrome (RLS) and cardiovascular diseases. However, the risk of cardiovascular events in patients ...with secondary RLS due to end‐stage renal disease (ESRD) is unclear. Our aim was to examine whether ESRD patients with RLS had an increased risk of cardio/cerebrovascular events and mortality.
Methods
In all, 1093 ESRD patients were recruited between 2009 and 2010. The diagnosis and severity of RLS were assessed in a face‐to‐face interview. The occurrence of cardio/cerebrovascular events and death were confirmed by medical record review. The association between RLS and the outcomes of interest was examined using an adjusted multivariate Cox regression model.
Results
After a mean follow‐up period of 3.7 ± 0.8 years, ESRD patients with RLS had a significantly higher risk of developing cardiovascular events and strokes adjusted hazard ratio (aHR) 2.82, 95% confidence interval (CI) 2.02–4.11, and aHR 2.41, 95% CI 1.55–3.75, respectively compared with patients without RLS. Increasing RLS severity was associated with an increasing likelihood of cardiovascular events mild RLS severity, aHR 1.71 (95% CI 1.02–2.87); moderate, 2.79 (1.64–4.66); severe, 2.85 (1.99–4.46) and strokes mild, 1.89 (0.87–4.16); moderate, 2.42 (1.50–3.90); severe, 2.64 (1.49–4.91) in a dose‐dependent manner. RLS also increased the risk of total mortality in patients with ESRD aHR 1.53 (95% CI 1.07–2.18), P = 0.02; this association attenuated slightly after stratification by individual RLS severity category mild RLS severity, aHR 1.44 (95% CI 0.78–2.67); moderate, 1.49 (0.98–2.55); severe, 2.03 (0.93–4.45).
Conclusions
ESRD patients with RLS demonstrated an increased likelihood of cardio/cerebrovascular events and mortality.
We present the first systematic analysis for new particle formation (NPF), growth and shrinkage of new particles at four different sites in subtropical central Taiwan. A total of 14 NPF events were ...identified from 137 days of ambient measurements during a cold and warm season. The measured formation rates of 10 nm particles (J sub(10)) and growth rates were in the range of 4.4-30 cm super(-3) s super(-1) and 7.4-24 nm h super(-1), respectively. The onset of NPF events coincided with decreases of condensation sink (CS) and increases of SO sub(2) under enhanced atmospheric mixing and dilution. However, the lower or comparable SO sub(2) on event days than on non-event days suggests that SO sub(2) was not a limiting factor for NPF. On non-event days, the particle number concentrations were mostly driven by traffic emissions. We also observed shrinkage of new particles, the reversal of growth, during five out of the identified secondary formation. UFP particles events. In intense cases, the grown particles shrank back to the smallest measurable size of similar to 10 nm, thereby creating a unique "arch-like" shape in the size distribution contour plot. The particle shrinkage rates ranged from -5.1 to -7.6 nm h super(-1). The corresponding particle volume losses suggest that a notable fraction of the condensable species that contributed to growth was semi-volatile. The particle shrinkage was related to enhanced atmospheric dilution, high ambient temperature and low relative humidity, thus favoring the evaporation of semi-volatile species from the particulate phase to the gas phase. Our observations show that the new particle growth could be a reversible process, in which the evaporating semi-volatile species are important for the growth of new particles to sizes of environmental health concerns.
Background and purpose
Recent genome‐wide association studies have shown associations between multiple genetic variants and primary restless legs syndrome (RLS). Their roles in end stage renal ...disease (ESRD) related secondary RLS are not clear and studies in Asian populations are scarce. The association between candidate genetic variants and uremic RLS was investigated in a large cohort of Taiwanese dialysis patients.
Methods
Sixteen RLS‐related genetic variants at six loci, including MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, TOX3/BC034767 and the intergenic region of chromosome 2p14, in a total of 993 ESRD patients (259 subjects with and 734 subjects without RLS) were genotyped using TaqMan® genotyping assays. Multivariate logistic regression analysis was used to test for associations between the genotypes and RLS in ESRD. Power calculations were completed using the CATs Genetic Power Calculator with settings of a multiplicative genetic model.
Results
A modest association between the PTPRD variant rs4626664 and uremic RLS (odds ratio 1.52, 95% CI 1.03–2.23, P = 0.03) and a trend that TOX3/BC034767 variant rs3104767 may associate with the occurrence of RLS were observed in our dialysis population (odds ratio 1.74, 95% CI 0.97–3.11, P = 0.06). No associations between other genetic variants and risk and severity of RLS were observed in our ESRD cohort.
Conclusions
The genetic variants of primary RLS candidate genes did not play a major role in our uremic RLS populations. The ethnic difference and heterogeneous etiologies underlying renal failure may partly explain the minor genetic contribution to uremic RLS in our populations. Further studies for other ethnicities will be of worth.
Backgrounds
Diabetes mellitus (DM) is a common endocrine disorder and an increasing epidemic worldwide. Proportional diabetic patients eventually develop cutaneous diseases.
Objectives
This study ...determined the statistical association of cutaneous manifestations and DM as well as the DM‐associated cutaneous manifestations in elderly male residents.
Methods
A cross‐sectional study was conducted in a Veterans Home in Taiwan. The cutaneous manifestations and major systemic diseases of the residents were recorded separately. Univariate logistic regression and multivariate analysis after adjustment for age, body mass index and significant major systemic diseases provided odds ratios and P values for the statistical association.
Results
A total of 313 male residents (age ≥65 years) were recruited, including 70 (22.4%) with DM. Their most common cutaneous manifestations included fungal infection (77%) and brown spots on the legs (38.3%). Chronic ulcers adjusted odds ratios (AOR 4.90, 95%CI: 1.82–13.19; P = 0.002), brown spots on the legs (AOR 6.82, 95%CI: 3.60–12.89; P < 0.001) and pruritus (AOR 12.86, 95%CI: 4.40–37.59; P < 0.001) were significantly associated with DM. The diabetic residents were inclined to have chronic ulcers, brown spots on the legs and pruritus at a 7.46‐fold higher risk (AOR 7.46, 95%CI: 3.86–14.43; P < 0.001). The diabetic residents exhibited marginally higher risks of bacterial infection, scabies, or skin tags.
Conclusion
The DM‐associated cutaneous manifestations were chronic ulcers, brown spots on the legs, and pruritus. By observing clues of diabetic cutaneous features, a more complete condition of diabetic patients can be appreciated. The information is essential for providing appropriate treatment and key nursing points regarding the diabetes‐associated skin diseases.
This paper offers comments on a previously published paper, titled "Multiple criteria decision making (MCDM) methods in economics: an overview," by Zavadskas and Turskis (2011). The paper's authors ...made great efforts to summarize MCDM methods but may have failed to consider several important new concepts and trends in the MCDM field for solving actual problems. First, the traditional model assumes the criteria are independently and hierarchically structured; however, in reality, problems are often characterized by interdependent criteria and dimensions and may even exhibit feedback-like effects. Second, relatively good solutions from the existing alternatives are replaced by aspiration levels to fit today's competitive markets. Third, the emphasis in the field has shifted from ranking and selection when determining the most preferable approaches to performance improvement of existing methods. Fourth, information fusion techniques, including the fuzzy integral method, have been developed to aggregate the performances. Finally, the original fixed resources in multi-objective programming are divided such that both decision and objective spaces are changeable. In this paper, we add new concepts and provide comments that could be thought of as an attempt to complete the original paper.
Organisations need to develop long-term strategies to ensure they incorporate innovation for environmental sustainability (IES) to remain competitive in the market. This can be challenging given the ...high level of uncertainty regarding the future (e.g., following the COVID pandemic). Supplier selection is an important decision that organisations make and can be designed to support IES. While the literature provides various criteria in the field of IES strategies, it does not identify the criteria which can be utilised to assist organisations in their supplier selection decisions. Moreover, the literature in this field does not consider uncertainty related to the occurrence of possible future events which may influence the importance of these criteria. To address this gap, this paper develops a novel criteria decision framework to assist supplier evaluation in organisations, taking into consideration different events that may occur in the future. The framework that combines three decision-making methods: the stratified multi-criteria decision-making method, best worst method, and technique for order of preference by similarity to ideal solution. The framework, proposed in this paper, can also be adopted to enable effective and sustainable decision making under uncertainty in various fields.
Familial amyloid polyneuropathy (FAP) due to amyloidogenic transthyretin (TTR) is often associated with impairment of thermonociceptive functions. This study investigated skin innervation and its ...clinical significance in genetically defined FAP due to a hot-spot Ala97Ser TTR mutation (Ala97Ser).
Skin biopsies were performed on the distal leg of patients with Ala97Ser, and intraepidermal nerve fiber (IENF) densities were quantified.
There were 19 unrelated patients with Ala97Ser manifesting a late-onset (59.47 +/- 5.70 years) generalized neuropathy with disabling motor, sensory, and autonomic symptoms. Against a background of a slowly progressive course, 7 patients (36.8%) exhibited additional rapid declines in neurologic deficits, which were associated with elevation of the protein content in the CSF (p < 0.001). The IENF density was markedly reduced in Ala97Ser patients compared to age- and gender-matched controls (0.99 +/- 1.11 vs 8.31 +/- 2.87 fibers/mm, p < 0.001). Skin denervation was present in all patients and was lower in patients with a higher disability grade (0.17 +/- 0.26 vs 1.37 +/- 1.16 fibers/mm, p = 0.003). Albuminocytologic dissociation in the CSF was observed in 14 patients (73.7%), and the IENF density was negatively correlated with the CSF protein concentration (p = 0.015).
Skin denervation was common in Ala97Ser, and degeneration of cutaneous nerve terminals was correlated with the severity of clinical phenotypes and the level of CSF protein.
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