Elevated markers of DNA damage and senescence are associated with the progression of albuminuria and restrictive lung disease in patients with type 2 diabetes.

BACKGROUND: This study was conducted to investigate the cascade involving DNA damage, senescence, and senescence-associated secretory phenotype (SASP) in experimental diabetes and in a four-year follow-up study in patients with pre-diabetes and type 2 diabetes. METHODS: Kidney, lung, and liver were studied in 4 months diabetic db/db mice and age-matched controls for the presence of DNA damage and fibrosis. DNA damage (comet-tail-length and ɤH2Ax-positivity in white blood cells), urinary p21-excretion, and plasma IL-6 and TGF-ß1 were determined from 115 healthy participants, 34 patients with pre-diabetes and 221 with type 2 diabetes. Urinary albumin-creatinine-ratio, lung function, and transient elastography of the liver were performed in a prospective follow-up study over 4 years. FINDINGS: db/db mice showed an increased nuclear ɤH2AX signal in all tissues as compared to the background control. Markers for DNA damage, senescence, and SASP were increased in patients with diabetes. The presence of nephropathy, restrictive lung disease (RLD), and increased liver stiffness was in a cross-sectional design associated with increased markers for DNA damage, senescence, and SASP. The progression of nephropathy over 4 years was predicted by increased DNA damage, senescence, and SASP, while the progression of RLD was associated with increased DNA damage and IL-6 only. The progression of liver stiffness was not associated with any of these parameters. HbA1c was not predictive for progression. INTERPRETATION: In db/db mice, the cascade of DNA damage is associated with diabetes-related complications. In patients with diabetes, the progression of complications in the kidney and lung is predicted by markers reflecting DNA damage, and senescence-triggered organ fibrosis. FUNDING: This work was supported by the German Research Foundation (DFG) in the CRC 1118 and CRC 1158, by the GRK DIAMICOM, by the German Center for Diabetes Research (DZD e.V.), and by the Ministry of Science, Research and the Arts, Baden-Württemberg (Kompetenznetzwerk Präventivmedizin).

Reliably Assessing Duration of Protection for COVID-19 Vaccines

Decision-making about booster dosing for COVID-19 vaccine recipients hinges on reliable methods for evaluating the longevity of vaccine protection. We show that modeling of protection as a piecewise linear function of time since vaccination for the log hazard ratio of the vaccine effect provides more reliable estimates of vaccine effectiveness at the end of an observation period and also more reliably detects plateaus in protective effectiveness as compared with the traditional method of estimating a constant vaccine effect over each time period. This approach will be useful for analyzing data pertaining to COVID-19 vaccines and other vaccines where rapid and reliable understanding of vaccine effectiveness over time is desired.

No short-term effects of calorie-controlled Mediterranean or fast food dietary interventions on established biomarkers of vascular or metabolic risk in healthy individuals

BACKGROUND/OBJECTIVES: This study addressed the question whether the composition of supposedly 'healthy' or 'unhealthy' dietary regimes has a calorie-independent short-term effect on biomarkers of metabolic stress and vascular risk in healthy individuals. SUBJECTS/METHODS: Healthy male volunteers (age 29.5 +/- 5.9 years, n = 39) were given a standardized baseline diet for two weeks before randomization into three groups of different dietary regimes: fast food, Mediterranean and German cooking style. Importantly, the amount of calories consumed per day was identical in all three groups. Blood samples were analyzed for biomarkers of cardiovascular risk and metabolic stress after two weeks of the baseline diet and after two weeks of the assigned dietary regime. RESULTS: No dietary intervention affected the metabolic or cardiovascular risk profile when compared in-between groups or compared to baseline. Subjects applied to the Mediterranean diet showed a statistically significant increase of uric acid compared to baseline and compared to the German diet group. Plasma concentrations of urea were significantly higher in both the fast food group and the Mediterranean group, when compared to baseline and compared to the German diet group. No significant differences were detected for the levels of vitamins, trace elements or metabolic stress markers (8-hydroxy-2-deoxyguanosine, malondialdehyde and methylglyoxal, a potent glycating agent). Established parameters of vascular risk (e.g. LDL-cholesterol, lipoprotein(a), homocysteine) were not significantly changed in-between groups or compared to baseline during the intervention period. CONCLUSIONS: The calorie-controlled dietary intervention caused neither protective nor harmful short-term effects regarding established biomarkers of vascular or metabolic risk. When avoiding the noxious effects of overfeeding, healthy individuals can possess the metabolic capacity to compensate for a potentially disadvantageous composition of a certain diet.

No short-term effects of calorie-controlled Mediterranean or fast food dietary interventions on established biomarkers of vascular or metabolic risk in healthy individuals

BACKGROUND/OBJECTIVES: This study addressed the question whether the composition of supposedly 'healthy' or 'unhealthy' dietary regimes has a calorie-independent short-term effect on biomarkers of metabolic stress and vascular risk in healthy individuals. SUBJECTS/METHODS: Healthy male volunteers (age 29.5 +/- 5.9 years, n = 39) were given a standardized baseline diet for two weeks before randomization into three groups of different dietary regimes: fast food, Mediterranean and German cooking style. Importantly, the amount of calories consumed per day was identical in all three groups. Blood samples were analyzed for biomarkers of cardiovascular risk and metabolic stress after two weeks of the baseline diet and after two weeks of the assigned dietary regime. RESULTS: No dietary intervention affected the metabolic or cardiovascular risk profile when compared in-between groups or compared to baseline. Subjects applied to the Mediterranean diet showed a statistically significant increase of uric acid compared to baseline and compared to the German diet group. Plasma concentrations of urea were significantly higher in both the fast food group and the Mediterranean group, when compared to baseline and compared to the German diet group. No significant differences were detected for the levels of vitamins, trace elements or metabolic stress markers (8-hydroxy-2-deoxyguanosine, malondialdehyde and methylglyoxal, a potent glycating agent). Established parameters of vascular risk (e.g. LDL-cholesterol, lipoprotein(a), homocysteine) were not significantly changed in-between groups or compared to baseline during the intervention period. CONCLUSIONS: The calorie-controlled dietary intervention caused neither protective nor harmful short-term effects regarding established biomarkers of vascular or metabolic risk. When avoiding the noxious effects of overfeeding, healthy individuals can possess the metabolic capacity to compensate for a potentially disadvantageous composition of a certain diet.

Effect of suture selection on the rate of suture or mesh erosion and surgery failure in abdominal sacrocolpopexy.

OBJECTIVE: : To determine if suture type used for mesh attachment in abdominal sacrocolpopexy increases the rate of erosion/infection. METHODS: : Two groups were temporally divided from June 1996 to May 2001 where braided permanent sutures (2-0 Ethibond, Ethicon, Somerville, New Jersey) were exclusively used for graft placement (n = 161) and from August 2001 to May 2006 where exclusively monofilament delayed absorbable (2-0 PDS, Ethicon) was used (n = 254). Data were analyzed for demographics, medical history, presenting/postoperative physical examination, concomitant surgeries, and complications. RESULTS: : Mesh/suture exposure rate was 3.7% (6/161) with Ethibond. There were no erosions with PDS (P = 0.002). Colpopexy failure was 1.7% (2/116) with Ethibond and 0% (0/235) with PDS (P = 0.11). CONCLUSIONS: : Delayed absorbable, monofilament suture appears to reduce the risk of graft/suture erosion without increasing surgical failure.

Perisurgical smoking cessation and reduction of postoperative complications.

OBJECTIVE: The purpose of this study was to determine if a perisurgical smoking cessation program reduces smoking-related postoperative complications in urogynecologic surgery. STUDY DESIGN: A review of patients that underwent pelvic reconstructive surgery from 1998 to 2003 was performed. All smokers underwent a perisurgical smoking cessation program of their choice for at least 1 month before surgery, and continued for 1 month after surgery. Complications unrelated to smoking (cystotomy, enterotomy, urethral obstruction, etc) were excluded in the smoking-potentiated complications. Problems considered to be potentiated by smoking were: wound, pulmonary, cardiac, and febrile morbidity. RESULTS: Eight hundred eighty-seven patients were included. There were 233 smoker cessation patients (SC) and 654 nonsmokers (NS). The total number of complications in the SC group was 61 (61/233, 26%) compared with 172 (172/654, 29%) in the NS group: (chi-square, P = .97). When looking at smoking-potentiated complications only, there were 34 (34/61, 56%) patients in the SC group and 90 (90/172, 52%) in the NS group (chi-square, P = .75). CONCLUSION: There are no differences in smoking-potentiated complications between nonsmoking patients and patients who undergo a perisurgical smoking cessation program.