Photoinduced decarboxylative germylation of α-fluoroacrylic acids: access to germylated monofluoroalkenes.

Herein, a novel strategy is presented for the photoinduced decarboxylative and dehydrogenative cross-coupling of a wide range of α-fluoroacrylic acids with hydrogermanes. This methodology provides an efficient and robust approach for producing various germylated monofluoroalkenes with excellent stereoselectivity within a brief photoirradiation period. The feasibility of this reaction has been demonstrated through gram-scale reaction, conversion of germylated monofluoroalkenes, and modification of complex organic molecules.

Effect of ultrafiltration on cerebral small-vessel disease and related outcomes in hemodialysis.

Background: Increasing evidence suggests a high prevalence of cerebral small-vessel disease (CSVD) in hemodialysis patients. Variable ultrafiltration during hemodialysis may contribute to brain lesions by inducing hemodynamic instability. We aimed to investigate the effect of ultrafiltration on CSVD and relative outcome in this population. Methods: In a prospective cohort of maintenance hemodialysis adults, three features of CSVD including cerebral microbleed (CMB), lacunae and white matter hyperintensity (WMH) were measured by brain magnetic resonance imaging. Ultrafiltration parameters included the difference between annual average ultrafiltration volume (UV, kg) and 3%-6% of dry weight (kg), respectively, and the percentage of UV to dry weight (UV/W). The effect of ultrafiltration on CSVD and the risk of cognitive decline were investigated by multivariate regression analysis. Cox proportional hazards model was used to assess mortality over 7 years of follow-up. Results: In the 119 study subjects, the frequency of CMB, lacunae and WMH was 35.3%, 28.6% and 38.7%, respectively. All ultrafiltration parameters were associated with the risk of CSVD in the adjusted model. There was a 37%, 47% and 41% greater risk of CMB, lacunae, and WMH, respectively, per 1% increment of UV/W. Ultrafiltration showed different effects on different distributions of CSVD. Restricted cubic splines depicted a linear relationship between UV/W and the risk of CSVD. At follow-up, lacunae and WMH were associated with cognitive decline, CMB and lacunae were associated with all-cause mortality. Conclusions: UV/W was associated with the risk of CSVD in hemodialysis. Reducing UV/W might protect hemodialysis patients from CSVD and subsequent cognitive decline and mortality.

Increased Premature Cerebral Small Vessel Diseases in Dialysis Patients: A Retrospective Cross-Sectional Study.

BACKGROUND: Growing data indicate a higher prevalence of cerebrovascular diseases in patients with ESRD. Cerebral small-vessel disease (CSVD) is an important risk factor of stroke and dementia. A comprehensive assessment of CSVD in a dialysis population is needed. METHODS: In this retrospective cross-sectional study, we enrolled 179 dialysis patients and 351 controls matched by sex and age with normal serum creatinine. The presence and locations of 3 main features of CSVD in dialysis patients, including lacunes, cerebral microbleeds (CMBs), and white matter hyperintensities (WMHs), were evaluated with brain magnetic resonance imaging and compared with controls. Univariate and multivariate analyses were performed to identify risk factors. RESULTS: Compared with controls, the prevalence of CSVD was significantly increased in dialysis patients (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.26-5.62). Among them, risks of CMBs and WMHs were increased in dialysis (OR 4.01, 95% CI 1.78-9.42; 3.91, 95% CI 1.67-9.15), except for lacunes. The age of subjects with CSVD detected was significantly younger in the dialysis group (p = 0.002). Unlike controls, basal ganglia were most affected by lacunes and CMBs in dialysis patients. In dialysis patients, multivariate analysis further revealed that aging, smoking, and hyperlipidemia were significantly associated with CSVD, while dialysis modality was not significant. CONCLUSION: We demonstrated a higher prevalence and early-onset tendency of CSVD in dialysis patients, especially for CMBs and WMHs. Dialysis patients showed different patterns and associated factors for CSVD.

Cerebral microbleeds and their influence on cognitive impairment in Dialysis patients.

Cerebral microbleeds (CMBs) in dialysis patients have recently attracted much attention, and the different locations of CMBs indicate different pathological processes. Previous studies on the relationship between CMBs and cognitive impairment (CI) in the general population and in dialysis patients have reported controversial results. A total of 180 chronic dialysis patients were enrolled in our study. Based on brain magnetic resonance imaging (MRI) analysis of CMBs, the patients were divided into 4 groups (without-CMBs group, strictly lobar group, strictly deep group, and mixed group). A wide range of cognitive tests was administered to evaluate cognitive function. The risk factors for CMBs were explored, and the correlation between CMB distribution and CI was investigated by regression analysis. The prevalence of CMBs was 32.8% in the total study population, 36.1% in the haemodialysis (HD) subgroup and 26.2% in the peritoneal dialysis (PD) PD subgroup. Sixteen subjects (8.9%) were classified as the lobar group, 12 subjects (6.7%) as the mixed group, and 31 subjects (17.2%) as the deep group. A significant association was shown between deep CMBs and impaired cognitive function, involving overall cognitive function, memory, language ability and executive function. Deep CMBs were significantly associated with dialysis vintage, mean arterial pressure (MAP) and lacunar infarcts number, while deep CMBs showed no correlation with dialysis modality and current heparin medication. Deep CMBs are closely associated with global and specific CI in dialysis patients. Blood pressure control may prevent deep CMBs and their associated CI.

Carotid intima-media thickness relative to cognitive impairment in dialysis patients, and their relationship with brain volume and cerebral small vessel disease.

BACKGROUND: Carotid intima-media thickness (cIMT) is considered a risk factor for and predictor of cerebrovascular disease. In this study, we explored the contribution of cIMT to cognitive impairment (CI) in dialysis patients and the role of cerebral small vascular disease (CSVD) and brain atrophy in this process. METHODS: Cognitive function was assessed using a comprehensive cognitive test battery. CSVD and brain volume were assessed by magnetic resonance imaging, and cIMT was measured by ultrasonography. Multivariable analysis and mediation were used to explore the relevant relationships among cIMT, CI, CSVD and brain volume. RESULTS: Seventy-three dialysis patients were enrolled. Approximately 54.8% were diagnosed with increased cIMT. The increased cIMT group was older and had lower serum albumin and creatinine levels than the normal cIMT group. There was no difference in the CSVD prevalence between the different cIMT groups. Patients in the normal, unilaterally and bilaterally increased cIMT subgroups demonstrated a gradual decrease in brain-matter volume and degenerate cognitive function. cIMT was related to cognitive function and gray-/white-matter volume. Increased cIMT was associated with a significantly increased risk of a reduced Mini Mental State Examination/Montreal Cognitive Assessment score and Trail A/B time delay. Mediation analysis showed that CI was mediated by brain-matter volume but not by CSVD. CONCLUSION: Increased cIMT was an independent risk factor for impairment of global cognitive function, memory, and executive function. The impact of cIMT on cognition was not induced by CSVD but by brain atrophy. cIMT may be a useful tool for screening patients at high risk of CI in the dialysis population.

Membranous nephropathy occurring with type 2 diabetes mellitus
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BACKGROUND: The incidence of type 2 diabetes mellitus (T2DM) is increasing, and membranous nephropathy (MN) occurs frequently with T2DM. We investigated the clinicopathological features and outcomes of patients with T2DM and MN. METHODS: A total of 137 patients with biopsy-proven MN and T2DM were enrolled in this retrospective study. Another 100 MN patients without diabetes mellitus served as a control group. The clinicopathological features, treatment responses, and outcomes were analyzed and compared between groups. RESULTS: According to the renal biopsy findings, isolated MN (D group) was observed in 86 patients, and MN superimposed on diabetic nephropathy (DN) (DN group) was observed in 51 patients. The mean age at the time of renal biopsy and the rate of hypertension in patients with MN were higher than in the control group. Male gender (odds ratio (OR), 2.887; 95% CI, 1.244 - 6.702), duration of diabetes (OR, 1.009; 95% CI, 1.001 - 1.016,), and diabetic retinopathy (OR, 2.862; 95% CI, 1.219 - 6.721) were independent predictors of DN. Lesions due to global glomerulosclerosis, interstitial fibrosis/tubular atrophy (IFTA), and the afferent arterioles were more severe in patients with diabetic MN. There were no differences in the rates of complete remission (CR) between the D and control groups. CONCLUSIONS: Diabetic MN usually presents in ageing and clinically hypertensive patients and is associated with severe global glomerulosclerosis, IFTA, and afferent arterial lesions histologically. Patients with pure MN with DM can frequently achieve remission. Gender (male), duration of diabetes, and diabetic retinopathy may serve as indicators of DN.
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Product wastage from modern human growth hormone administration devices: a laboratory and computer simulation analysis.

BACKGROUND: Treatment of growth hormone disorders typically involves daily injections of human growth hormone (GH) over many years, incurring substantial costs. We assessed the extent of undesired GH loss due to leakage in the course of pen preparation prior to injection, and differences between the prescribed dose, based on patient weight, and the actual delivered dose based on pen dosing increments in five GH administration devices. METHODS: Norditropin® prefilled FlexPro®, NordiFlex®, NordiLet®, and durable NordiPen®/SimpleXx® 5 mg pens (Novo Nordisk A/S, Bagsværd, Denmark) and durable Omnitrope® Pen-5 devices (Sandoz, Holzkirchen, Germany) were tested (n = 40 for each device type). Product wastage was measured in accordance with validated protocols in an ISO (International Organization for Standardization) 11608-1 and Good Manufacturing Practice compliant laboratory. The average mass of wasted GH from each device type was measured in simulations of dripping with the needle attached prior to injection and while setting a dose. Statistical significance (P < 0.05) was confirmed by Student's t-test, and a model was constructed to estimate mean annual GH wastage per patient in cohorts of pediatric patients with GH disorders. RESULTS: Mean GH mass wasted with the needle on prior to injection was 0.0 µg with Norditropin pens, relative to 98 µg with Omnitrope Pen-5. During dose dialing, 0.0-2.3 µg of GH was lost with Norditropin pens versus 0.8 µg with Omnitrope Pen-5. All Norditropin and Omnitrope device comparisons were statistically significant. Modeling GH wastage in a US cohort showed 5.5 mg of annual GH wastage per patient with FlexPro versus 43.6 mg with Omnitrope, corresponding to 7-8 additional pens per patient annually. CONCLUSION: Overall, Norditropin pens resulted in significantly less wastage than the Omnitrope Pen-5. The study suggests that GH devices of the same nominal volume exhibit differences that may affect the frequency of GH prescription refills required to remain adherent to therapy.

Effect of LY294002 on adriamycin-induced epithelial-mesenchymal transition in human breast carcinoma cells.

OBJECTIVE: To study the effect of LY294002 on the adriamycin- induced epithelial-mesenchymal transition in human breast carcinoma cells. METHODS: Human breast carcinoma cells MCF-7 was cultured in vitro and then exposed to adriamycin with or without LY294002. The protein expression levels of Akt, phosphorylated-Akt (p-Akt), Snail, and E-cadherin was detected by Western blot analysis. The mRNA expressions of Snail and E-cadherin were determined by RT-PCR. RESULTS: Adriamycin significantly increased the protein expression of Snail and depressed the protein expression of E-cadherin (P<0.05). The pre-treatment with LY294002 significantly reversed the changes of activities and levels of the above proteins (P<0.05). CONCLUSION: LY294002 could reverse the adriamycin-induced epithelial-mesenchymal transition in human breast carcinoma cells by regulating the expressions of Snail and E-cadherin through suppressing PI3K/Akt signaling pathway.