Background
Blunt traumatic abdominal wall hernias (TAWHs) are rare but require a variety of operative techniques to repair including bone anchor fixation (BAF) when tissue tears off bony structures. ...This study aimed to provide a descriptive analysis of BAF technique for blunt TAWH repair. Bone anchor fixation and no BAF repairs were compared, hypothesizing increased hernia recurrence with BAF repair.
Methods
A secondary analysis of the WTA blunt TAWH multicenter study was performed including all patients who underwent repair of their TAWH. Patients with BAF were compared to those with no BAF with bivariate analyses.
Results
176 patients underwent repair of their TAWH with 41 (23.3%) undergoing BAF. 26 (63.4%) patients had tissue fixed to bone, with 7 of those reinforced with mesh. The remaining 15 (36.6%) patients had bridging mesh anchored to bone. The BAF group had a similar age, sex, body mass index, and injury severity score compared to the no BAF group. The time to repair (1 vs 1 days, P = .158), rate of hernia recurrence (9.8% vs 12.7%, P = .786), and surgical site infection (SSI) (12.5% vs 15.6%, P = .823) were all similar between cohorts.
Conclusions
This largest series to date found nearly one-quarter of TAWH repairs required BAF. Bone anchor fixation repairs had a similar rate of hernia recurrence and SSI compared to no BAF repairs, suggesting this is a reasonable option for repair of TAWH. However, future prospective studies are needed to compare specific BAF techniques and evaluate long-term outcomes including patient-centered outcomes such as pain and quality of life.
The chiral acyclic "pa" ligand (pa = picolinic acid) H2CHXdedpa (N4O2) and two NI-containing dedpa analogues (H2CHXdedpa-N,N'-propyl-2-NI, H2dedpa-N,N'-propyl-2-NI, NI = nitroimidazole) were studied ...as chelators for copper radiopharmaceuticals (CHX = cyclohexyl, H2dedpa = 1,2-carboxypyridin-2-ylmethylaminoethane). The hexadentate ligand H2CHXdedpa was previously established as a superb system for 67/68Ga radiochemistry. The solid state X-ray crystal structures of Cu(CHXdedpa-N,N'-propyl-2-NI) and Cu(dedpa-N,N'-propyl-2-NI) reveal the predicted hexadentate, distorted octahedral binding of the copper(ii) ion. Cyclic voltammetry of Cu(dedpa-N,N'-propyl-2-NI) shows that there is one reversible couple associated with the NI redox, and one irreversible but reproducible couple attributed to the Cu(ii)/Cu(i) redox cycle. Quantitative radiolabeling (>99%) of CHXdedpa2- and (dedpa-N,N'-propyl-2-NI)2- with 64Cu was achieved under fast and efficient labeling conditions (10 min, RT, 0.5 M sodium acetate buffer, pH 5.5) at ligand concentrations as low as 10-6 M. In vitro kinetic inertness studies of the 64Cu labelled complexes were studied in human serum at 37 degree C over 24 hours; 64Cu(CHXdedpa) was found to be 98% stable compared to previously investigated 64Cu(dedpa) which was only 72% intact after 24 hours.
We use cosmic microwave background (CMB) temperature maps from the 500 deg$^{2}$ SPTpol survey to measure the stacked lensing convergence of galaxy clusters from the Dark Energy Survey (DES) Year-3 ...redMaPPer (RM) cluster catalog. The lensing signal is extracted through a modified quadratic estimator designed to be unbiased by the thermal Sunyaev-Zel{'}dovich (tSZ) effect. The modified estimator uses a tSZ-free map, constructed from the SPTpol 95 and 150 GHz datasets, to estimate the background CMB gradient. For lensing reconstruction, we employ two versions of the RM catalog: a flux-limited sample containing 4003 clusters and a volume-limited sample with 1741 clusters. We detect lensing at a significance of 8.7$\sigma$(6.7$\sigma$) with the flux(volume)-limited sample. By modeling the reconstructed convergence using the Navarro-Frenk-White profile, we find the average lensing masses to be $M_{200m}$ = ($1.62^{+0.32}_{-0.25}$ stat. $\pm$ 0.04 sys.) and ($1.28^{+0.14}_{-0.18}$ stat. $\pm$ 0.03 sys.) $\times\ 10^{14}\ M_{\odot}$ for the volume- and flux-limited samples respectively. The systematic error budget is much smaller than the statistical uncertainty and is dominated by the uncertainties in the RM cluster centroids. We use the volume-limited sample to calibrate the normalization of the mass-richness scaling relation, and find a result consistent with the galaxy weak-lensing measurements from DES.
We use cosmic microwave background (CMB) temperature maps from the 500 deg(2) SPTpol survey to measure the stacked lensing convergence of galaxy clusters from the Dark Energy Survey (DES) Year-3 ...redMaPPer (RM) cluster catalog. The lensing signal is extracted through a modified quadratic estimator designed to be unbiased by the thermal Sunyaev-Zel'dovich (tSZ) effect. The modified estimator uses a tSZ-free map, constructed from the SPTpol 95 and 150 GHz data sets, to estimate the background CMB gradient. For lensing reconstruction, we employ two versions of the RM catalog: a flux-limited sample containing 4003 clusters and a volume-limited sample with 1741 clusters. We detect lensing at a significance of 8.7 sigma(6.7 sigma) with the flux (volume)-limited sample. By modeling the reconstructed convergence using the Navarro-Frenk-White profile, we find the average lensing masses to be M-200 m =(1.62(-0.25)(+0.35) stat. +/- 0.04 sys. and (1.28(-0.18)(+0.14) stat. +/- 0.03 sys. x 10(14) M-circle dot for the volume- and flux-limited samples, respectively. The systematic error budget is much smaller than the statistical uncertainty and is dominated by the uncertainties in the RM cluster centroids. We use the volume-limited sample to calibrate the normalization of the mass-richness scaling relation, and find a result consistent with the galaxy weak-lensing measurements from DES.
Depressive symptoms predominate in the course of bipolar disorder (BD) and there is an urgent need to evaluate novel application of repurposed compounds that act on pre-specified treatment targets. ...Several lines of reasoning suggest that nitrous oxide (N2O) is an ideal medication to study as a potential treatment and as a strategy to identify the underlying pathophysiology of bipolar depression. N2O is a potent cerebral vasodilator and there is compelling evidence of reduced frontal cerebral blood flow (CBF; i.e. hypoperfusion) in depression. Therefore, N2O may increase CBF and thereby improve symptoms of depression. The goal of this randomized, double-blind trial is to study the effect of a single administration of N2O versus the active comparator midazolam on mood and CBF in adults with treatment-resistant bipolar depression.
Participants with BD-I/-II currently experiencing a major depressive episode will be randomized to one of two conditions (n = 20/group): 1) inhaled N2O plus intravenous saline, or 2) inhaled room air plus intravenous midazolam. Montgomery-Asberg Depression Rating Scale scores will serve as the primary endpoint. CBF will be measured via arterial spin labelling magnetic resonance imaging.
N2O is a potential novel treatment for bipolar depression, as it causes cerebral vasodilation. This proof-of-concept study will provide valuable information regarding the acute impact of N2O on mood and on CBF. If N2O proves to be efficacious in future larger-scale trials, its ubiquity, safety, low cost, and ease of use suggest that it has great potential to become a game-changing acute treatment for bipolar depression.
Inactivation of the p53 tumor suppressor gene is a commonevent in the development of colon cancer. We usedata collected as part of a multicenter
case-control study of colon cancer to evaluate ...associations between p53 mutations and diet and lifestyle factors. p53 mutational status was determined for 1458 incident cases of colon cancer using single-strand conformational polymorphism/sequencing
of exons 5–8. We determined associations among those with and without mutations compared with population-based controls ( N = 2410) and to cases with p53 mutations compared with cases without p53 mutations. Associations also were examined by location and function of specific types of p53 mutations. p53 mutations were identified in tumors in 47.1% of cases; 81.9% of people with mutations had a missense mutation. Cases with
a p53 mutation were more likely to consume a Western-style diet, compared with controls odds ratio (OR), 2.03; 95% confidence
interval (CI), 1.53–2.69, than were cases who were p53 wild type (Wt), compared with controls (OR, 1.57;95% CI, 1.20–2.06).
Specific components of the Western-style diet, including diets with a high glycemic load (mutation versus control: OR, 1.48; 95% CI, 1.11–1.98 and Wt versus control: OR, 0.98; 95% CI, 0.75–1.28) and diets high in red meat, fast food, and trans- fatty acid (mutation versus control: OR, 1.92; 95% CI, 1.47–2.50 and Wt versus control: OR, 1.39; 95% CI, 1.08–1.80) appeared to be most strongly associated with p53 mutations. Diets with a high glycemic load (relative to lowest intake) were significantly associated with missense mutations
(OR, 1.69; 95% CI, 1.23–2.33 comparing p53+ to controls and OR, 1.72; 95% CI, 1.19–2.50 comparing cases p53+ to cases p53 Wt), as were diets high in red meat, fast food, and trans- fatty acids (OR, 1.92; 95% CI, 1.14–2.56 comparing p53+ to controls and OR, 1.40; 95% CI, 1.00–1.98 comparing cases p53 + to cases p53 Wt). Physical inactivity, large body mass index, cigarette smoking, using aspirin/nonsteroidal anti-inflammatory drugs, and
other dietary factors appeared to be comparably associated with colon cancer in those with and without p53 mutations. These data suggest that components of a Western-style diet such as high consumption of red meat and foods that
increase glycemic load are associated with a p53 disease pathway.
Background
The ATN classification system assumes a sequential model of disease progression. However, there are groups of individuals in the same ATN category that exhibit a predominance of ...abnormality (higher burden) of one of the biomarkers, creating heterogeneous ATN groups regarding pathological predominance. Thus, we tested the hypothesis that individuals clustered by ATN biomarker abnormality predominance may offer an alternative to groups defined using biomarkers cut‐offs.
Method
We assessed 103 cognitively impaired individuals(CDR> = 0.5) from the TRIAD cohort with available measures of plasma phosphorylated tau‐181, brain MRI, amyloid PET, and tau PET. We used the K‐means algorithm to stratify participants into three clusters. We compared the clusters on composite measures of memory, executive functioning, language, and visuospatial processing. To examine the utility of the discovered clusters, we compared them to traditional ATN categories in the prediction of neuropsychological measures. We did so by creating three categories: patients positive on all three ATN biomarkers, patients positive on two of the three biomarkers, and patients positive on either one or none. Additionally, we created an inflammation, amyloid and tau deposition probabilistic map anchored on young controls(n = 51, mean age = 23.74).
Result
We uncovered 3 clusters: an amyloid predominant (AP) cluster, a tau/phosphor‐tau predominant cluster (TP), and a cluster showing no predominance with low levels on all biomarkers (CN)(figure 1). Notably, levels of neurodegeneration and inflammation were similar between the AP and TP clusters. The AP cluster significantly differed from the CN cluster in memory only. Participants in the TP cluster had significantly lower scores in memory, executive functioning, language, and visuospatial processing than the other two clusters. In comparison, using threshold‐based ATN groups showed milder differences in memory and executive functioning, and no differences in language and visuospatial processing(figure 2). Furthermore, cluster membership moderated the relationship between various biomarkers, to the point of reversing the direction of correlation(figure 3).
Conclusion
Our results highlight the biological heterogeneity present within the Alzheimer’s disease continuum and that the pathological predominance of amyloid and tau is associated with different disease phenotypes. Approaching dementia patients with an eye on the predominance of pathology rather than cutoffs for abnormality may provide a better understanding of AD pathological subtypes.
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