Re‐establishment of cytoskeletal tensional homeostasis in lax tendons occurs through an actin‐mediated cellular contraction of the extracellular matrix

Cytoskeletal tensional homeostasis is known to be an important factor in controlling catabolic gene expression in tendon cells. Loss of cell tension in lax rat tail tendon fascicles (RTTfs) has been associated with an upregulation of MMP‐13 gene expression and protein synthesis. To determine the role of the actin cytoskeleton in re‐establishing tensional homeostasis in lax tendons, RTTfs were allowed to freely contract in vitro for 8 days. The cultured RTTfs contracted rapidly, reaching 50% of their initial length by 3 days. This contraction was associated with the presence of α‐smooth muscle actin positive cells within the tendon. Disruption of the actin network by cytochalasian D caused an immediate and significant elongation of the contracted RTTfs. Subsequent removal of the cytochalasian D re‐initiated the contraction process. When lax RTTfs were allowed to contract between fixed clamps in culture and become taut, they demonstrated a marked decrease in MMP‐13 staining intensity when compared to freely contracting RTTfs. The ability of native tendon cells to contract lax tendons and re‐establish their homeostatic “set point” with respect to collagenase production may be an important mechanism in the recovery of tendons elongated by injury, surgical positioning, or cyclic, viscoelastic creep secondary to repetitive exercise. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1695–1701, 2012     

Impact of measuring multiple or single occlusal lesions on estimates of diagnostic accuracy using fluorescence methods

Carious lesions can occur at different sites on the occlusal surfaces of teeth and may differ in appearance and severity. This study aimed to evaluate how scoring several lesions on occlusal surfaces, as opposed to only one representative lesion, affects estimates of reproducibility and accuracy of fluorescence-based devices. Thirty-six permanent teeth with 2-3 investigation sites (n = 82) were examined by two examiners using the laser fluorescence device DIAGNOdent pen (LF) and the fluorescence camera VistaProof (FC). Lesion depth was then assessed histologically in serial sections of the teeth. Intra-class-correlation coefficients (ICC) and areas under the ROC-curves were calculated for all investigation sites and for one randomly selected site per tooth. Comparing the reproducibility and the performance for the whole sample and the independent sites showed only a small effect or no effect. Measuring multiple sites on teeth with fluorescence devices only moderately influences performance compared to one site being investigated.     

The early decline in renal function in patients with type 1 diabetes and proteinuria predicts the risk of end-stage renal disease

The risk of end-stage renal disease (ESRD) remains high in patients with type 1 diabetes and proteinuria; however, little is known about the rate of decline in their renal function. To help determine this, we enrolled patients with type 1 diabetes and proteinuria whose estimated glomerular filtration rate (eGFR) was normal (equal to or above 60?ml/min per 1.73?m(2)). Using a minimum of five serial measurements of serum creatinine for 161 patients, we determined individual trajectories of eGFR change and the occurrence of ESRD during 5-18 years of follow-up. The rates were linear for 110 patients, for 24 the nonlinear rate was mild enough to satisfy a linear model, and the rates were clearly nonlinear for only 27 patients. Overall, in more than one-third of patients, the eGFR decline was less than 3.5?ml/min per 1.73?m(2) per year and the lifetime risk of ESRD could be considered negligible. In the remainder of patients, eGFR declined with widely different slopes and ESRD developed within 2 to 18 years. Based on up to 5 years observation, when renal function was within the normal range, the estimates of early eGFR slope predicted the risk of ESRD during subsequent follow-up better than the baseline clinical characteristics of glycated hemoglobin, blood pressure, or the albumin to creatinine ratio. Thus, the early slope of eGFR decline in patients with type 1 diabetes and proteinuria can be used to predict the risk of ESRD.     

Autophagy-regulating TP53INP2 mediates muscle wasting and is repressed in diabetes

A precise balance between protein degradation and synthesis is essential to preserve skeletal muscle mass. Here, we found that TP53INP2, a homolog of the Drosophila melanogaster DOR protein that regulates autophagy in cellular models, has a direct impact on skeletal muscle mass in vivo. Using different transgenic mouse models, we demonstrated that muscle-specific overexpression of Tp53inp2 reduced muscle mass, while deletion of Tp53inp2 resulted in muscle hypertrophy. TP53INP2 activated basal autophagy in skeletal muscle and sustained p62-independent autophagic degradation of ubiquitinated proteins. Animals with muscle-specific overexpression of Tp53inp2 exhibited enhanced muscle wasting in streptozotocin-induced diabetes that was dependent on autophagy; however, TP53INP2 ablation mitigated experimental diabetes-associated muscle loss. The overexpression or absence of TP53INP2 did not affect muscle wasting in response to denervation, a condition in which autophagy is blocked, further indicating that TP53INP2 alters muscle mass by activating autophagy. Moreover, TP53INP2 expression was markedly repressed in muscle from patients with type 2 diabetes and in murine models of diabetes. Our results indicate that TP53INP2 negatively regulates skeletal muscle mass through activation of autophagy. Furthermore, we propose that TP53INP2 repression is part of an adaptive mechanism aimed at preserving muscle mass under conditions in which insulin action is deficient.     

International survey study of attitudes towards robotic surgery

The field of robotic surgery is rapidly advancing both in terms of the surgical procedures performed and the potential applications of this technology. This survey study attempts to evaluate the opinions of the public regarding a number of issues in robotic surgery. A web-based survey study was constructed using the web-based software ??Kwiksurveys??. This survey was then advertised and distributed over the Internet to gain responders from a wide range of socio-economic groups and in a number of countries. Responses were collected over a six-month period. One-hundred and fifty-five participants took part in this survey study. The mean age of participants was 35.5?±?3.4?years. The majority of participants (52%) were either comfortable or totally comfortable with the current version of robotic surgery during which a surgeon in the same room controls instruments inside the patient. Sixty-eight percent of responders reported they would be very uncomfortable with the idea of not seeing the operating surgeon in person before or after surgery. Forty-five percent of participants reported they would consider the idea of an internal robot operating internally with little or no external scarring. This survey study has demonstrated that currently the public seem to be comfortable with the current version of robotic surgery, with the operating surgeon in the same room as the patient. The results of this survey study show that even with technical advances in robotic surgery, patients will still want to have contact with their operating surgeon.     

Early Progressive Renal Decline Precedes the Onset of Microalbuminuria and Its Progression to Macroalbuminuria

OBJECTIVE

Progressive decrease in the glomerular filtration rate (GFR), or renal decline, in type 1 diabetes (T1D) is observed in patients with macroalbuminuria. However, it is unknown whether this decline begins during microalbuminuria (MA) or normoalbuminuria (NA).

RESEARCH DESIGN AND METHODS

The study group (second Joslin Kidney Study) comprises patients with T1D and NA (n = 286) or MA (n = 248) who were followed for 4–10 years (median 8 years). Serial measurements (median 6, range 3–16) of serum creatinine and cystatin C were used jointly to estimate GFR (eGFRcr-cys) and assess its trajectories during follow-up.

RESULTS

Renal decline (progressive eGFRcr-cys loss of at least 3.3% per year) occurred in 10% of the NA and 35% of the MA (P < 0.001). In both groups, the strongest determinants of renal decline were baseline serum concentrations of uric acid (P < 0.001) and tumor necrosis factor receptor 1 or 2 (TNFR-1 or -2, P < 0.001). Other significant risk factors included baseline HbA_1c, age/diabetes duration, and systolic blood pressure. Relative impacts of these determinants were similar in NA and MA. Renal decline was not associated with sex or baseline serum concentration of TNF-α, IL-6, IL-8, IP-10, MCP-1, VCAM, ICAM, Fas, or FasL.

CONCLUSIONS

Renal decline in T1D begins during NA and it is determined by multiple factors, similar to MA. Thus, this early decline is the primary disease process leading to impaired renal function in T1D. Changes in albumin excretion rate, such as the onset of MA or its progression to macroalbuminuria, are either caused by or develop in parallel to the early renal decline.     

Preventable and non‐preventable risk factors for influenza transmission and hygiene behavior in German influenza households,pandemic season (H1N1) 2009/2010

Background To date, little is known about the role of behavioral risk factors for influenza transmission as well as hygiene behavior in the household setting during the influenza pandemic (H1N1) 2009. In a household‐based study conducted during 2008/2009, we identified several behavioral risk factors for influenza transmission; 30% of index patients and 30% of household contacts reported increased hand cleaning frequency in the week after symptom onset of the index patient. We conducted another household‐based study during the pandemic season 2009/2010. Methods We identified index patients with laboratory confirmed influenza infection and interviewed household members after illness day 8 of the index patient. Outcome was influenza‐like illness (ILI) in a household contact. Results We included 108 households. Overall secondary attack rate was 10·1% (27/267) and decreased with increasing age. Apart from being in close daily proximity with the index patient for at least 9 hours, no other behavioral risk factor was associated with secondary ILI. Of all index patients and household contacts, 49% and 55%, respectively, cleaned their hands more often in the week after symptom onset of the index patient (in comparison with 2008/2009 P‐value for both <0·01). Conclusions While the study was hampered by its relatively limited size, data suggest that a significantly larger proportion of influenza households practiced good hand hygiene compared to the last pre‐pandemic season. This may have led to a different risk factor profile and a delay of the time threshold necessary for transmission among household members with close contact.