Tumor suppressor PALB2 maintains redox and mitochondrial homeostasis in the brain and cooperates with ATG7/autophagy to suppress neurodegeneration.

The PALB2 tumor suppressor plays key roles in DNA repair and has been implicated in redox homeostasis. Autophagy maintains mitochondrial quality, mitigates oxidative stress and suppresses neurodegeneration. Here we show that Palb2 deletion in the mouse brain leads to mild motor deficits and that co-deletion of Palb2 with the essential autophagy gene Atg7 accelerates and exacerbates neurodegeneration induced by ATG7 loss. Palb2 deletion leads to elevated DNA damage, oxidative stress and mitochondrial markers, especially in Purkinje cells, and co-deletion of Palb2 and Atg7 results in accelerated Purkinje cell loss. Further analyses suggest that the accelerated Purkinje cell loss and severe neurodegeneration in the double deletion mice are due to excessive oxidative stress and mitochondrial dysfunction, rather than DNA damage, and partially dependent on p53 activity. Our studies uncover a role of PALB2 in mitochondrial homeostasis and a cooperation between PALB2 and ATG7/autophagy in maintaining redox and mitochondrial homeostasis essential for neuronal survival.

Incidence and outcomes of intraoperative vascular surgery consultations.

OBJECTIVE: Vascular surgeons may aid in primarily nonvascular procedures. Such activity has not been quantified, and hospital administrators may be unaware of the importance of vascular surgeons to support other hospital-based surgical programs. This study reviewed intraoperative consultations by vascular surgeons to support other surgical services. METHODS: Intraoperative vascular consultations were reviewed from January 2006 to January 2014 for consulting service, indication, and whether consultation occurred with advanced notice. Patient demographics, operative times, estimated blood loss, length of stay, and relative value units (RVUs) assigned for each consultation were also assessed. Consultations for trauma and iatrogenic injuries occurring outside the operating theater were excluded. RESULTS: Vascular surgeons performed 225 intraoperative consultations in support of procedures by nonvascular surgeons. Requesting services were surgical oncology (46%), orthopedics (17%), urology (11%), otolaryngology (7%), and others (19%). Reasons for consultation overlapped and included vascular reconstruction (53%), control of hemorrhage (39%), and assistance with difficult dissections (43%). Seventy-four percent were for intra-abdominal procedures, and venous (53%) and arterial (50%) problems were encountered equally with some overlap. Most patients were male (59%), overweight (56%; body mass index ≥25 kg/m(2)), had previous surgery (72%) and were undergoing elective procedures (89%). Mean total procedural anesthesia time was 9.4 hours, mean procedural operating time was 7.9 hours, and mean total and vascular-related estimated blood loss was 1702 mL and 327 mL, respectively. Mean length of stay was 14.7 days, mean intensive care unit stay was 2.9 days, and 30-day mortality was 6.2%. Mean nonvascular RVUs per operation were 46.0, and mean vascular RVUs per operation were 30.9. CONCLUSIONS: Unexpected intraoperative need for vascular surgical expertise occurs often enough that vascular surgeons should be regarded as an essential operating room resource to the general operating room, nonvascular surgeons, and their patients. Intraoperative vascular surgical consultation in support of other surgeons requires a high level of open technical operative skills and is time and labor intensive.

A Comparison of Venous versus Capillary Blood Samples when Measuring Blood Glucose Using a Point-of-Care, Capillary-Based Glucometer.

BACKGROUND: Blood glucose level (BGL) is routinely assessed by paramedics in the out-of-hospital setting. Most commonly, BGL is measured using a blood sample of capillary origin analyzed by a hand-held, point-of-care glucometer. In some clinical circumstances, the capillary sample may be replaced by blood of venous origin. Given most point-of-care glucometers are engineered to analyze capillary blood samples, the use of venous blood instead of capillary may lead to inaccurate or misleading measurements. HYPOTHESIS/PROBLEM: The aim of this prospective study was to compare mean difference in BGL between venous and capillary blood from healthy volunteers when measured using a capillary-based, hand-held, point-of-care glucometer. METHODS: Using a prospective observational comparison design, 36 healthy participants provided paired samples of blood, one venous and the other capillary, taken near simultaneously. The BGL values were similar between the two groups. The capillary group had a range of 4.3mmol/l, with the lowest value being 4.4mmol/l and 8.7mmol/l the highest. The venous group had a range of 2.7mmol/l, with the lowest value being 4.1mmol/l and 7.0mmol/l the highest.For the primary research question, the mean BGL for the venous sample group was 5.3mmol/l (SD = 0.6), compared to 5.6mmol/l (SD = 0.8) for the capillary group. This represented a statistically significant difference of 0.3mmol/l (P = .04), but it did not reach the a priori established point of clinical significance (1.0mmol/l). Pearson's correlation coefficient for capillary versus venous indicated moderate correlation (r = 0.42). CONCLUSION: In healthy, non-fasted people in a non-clinical setting, a statistically significant, but not clinically significant, difference was found between venous- and capillary-derived BGL when measured using a point-of-care, capillary-based glucometer. Correlation between the two was moderate. In this context, using venous samples in a capillary-based glucometer is reasonable providing the venous sample can be gathered without exposure of the clinician to risk of needle-stick injury. In clinical settings where physiological derangement or acute illness is present, capillary sampling would remain the optimal approach.