The goal of this article is to review the complex topic of total nasal reconstruction and present a wide range of options for completing this difficult surgical procedure.
Nasal reconstruction has a ...long history dating back thousands of years. Some historical techniques still exist today, including the paramedian forehead flap. The introduction of free tissue transfer and other pedicled flaps has provided multiple options for the reconstructive surgeon. The future of nasal reconstruction will include facial transplantation and likely bioengineered tissues.
The principles of nasal reconstruction have gone unchanged for decades; however, the techniques to meet the principles have. The current reconstructive methods of grafts, free flaps, and pedicled flaps used to replace lining, structure, and skin will likely be used for several years to come. However, the use of facial transplantation has proved effective and bioengineered tissues present an exciting future for organ replacement.
The central cholinergic system and the amygdala are important for motivation and mnemonic processes. Different cholinergic populations innervate the amygdala, but it is unclear how these projections ...impact amygdala processes. Using optogenetic circuit-mapping strategies in choline acetyltransferase (ChAT)-cre mice, we demonstrate that amygdala-projecting basal forebrain and brainstem ChAT-containing neurons can differentially affect amygdala circuits and behavior. Photo-activating ChAT terminals in vitro revealed the underlying synaptic impact of brainstem inputs to the central lateral division to be excitatory, mediated via the synergistic glutamatergic activation of AMPA and NMDA receptors. In contrast, stimulating basal forebrain inputs to the basal nucleus resulted in endogenous acetylcholine (ACh) release, resulting in biphasic inhibition-excitation responses onto principal neurons. Such response profiles are physiological hallmarks of neural oscillations and could thus form the basis of ACh-mediated rhythmicity in amygdala networks. Consistent with this, in vivo basal forebrain ChAT+ activation strengthened amygdala basal nucleus theta and gamma frequency rhythmicity, both of which continued for seconds after stimulation and were dependent on local muscarinic and nicotinic receptor activation, respectively. Activation of brainstem ChAT-containing neurons, however, resulted in a transient increase in central lateral amygdala activity that was independent of cholinergic receptors. In addition, driving these respective inputs in behaving animals induced opposing appetitive and defensive learning-related behavioral changes. Because learning and memory are supported by both cellular and network-level processes in central cholinergic and amygdala networks, these results provide a route by which distinct cholinergic inputs can convey salient information to the amygdala and promote associative biophysical changes that underlie emotional memories.
•Forebrain and brainstem ACh neurons differentially innervate distinct amygdala nuclei•Brainstem ACh neurons transiently excite CeL amygdala neurons through glutamate•Forebrain ACh neurons can synchronize BL activity via ACh receptor activation•Brainstem and forebrain amygdala inputs drive opposing learning-related behaviors
Aitta-aho et al. show that different cholinergic neuronal populations projecting to distinct amygdala nuclei coordinate local circuits and can reinforce approach and avoidance behavior. These results reveal separate mechanisms by which ACh populations can engage processes for inducing biophysical changes that underlie emotional memories.
Meningiomas are the most common primary intracranial tumors. There are no effective medical therapies for meningioma patients, and new treatments have been encumbered by limited understanding of ...meningioma biology. Here, we use DNA methylation profiling on 565 meningiomas integrated with genetic, transcriptomic, biochemical, proteomic and single-cell approaches to show meningiomas are composed of three DNA methylation groups with distinct clinical outcomes, biological drivers and therapeutic vulnerabilities. Merlin-intact meningiomas (34%) have the best outcomes and are distinguished by NF2/Merlin regulation of susceptibility to cytotoxic therapy. Immune-enriched meningiomas (38%) have intermediate outcomes and are distinguished by immune infiltration, HLA expression and lymphatic vessels. Hypermitotic meningiomas (28%) have the worst outcomes and are distinguished by convergent genetic and epigenetic mechanisms driving the cell cycle and resistance to cytotoxic therapy. To translate these findings into clinical practice, we show cytostatic cell cycle inhibitors attenuate meningioma growth in cell culture, organoids, xenografts and patients.
Despite increased use of irrigation to improve forage quality and quantity for grazing cattle (Bos taurus, Linnaeus), there is a lack of data that assess how irrigation practices influence nitrous ...oxide (N2O) emissions from urine‐affected soils. Irrigation effects on soil oxygen (O2) availability, a primary controller of N2O fluxes, is poorly understood. It was hypothesized that increased irrigation frequency would result in lower N2O emissions by increasing soil moisture and decreasing soil O2 concentrations. This would favor more N2O reduction to dinitrogen (N2). We examined effects of high (3‐d) versus low (6‐d) irrigation frequency with and without bovine urine addition to pasture. Nitrous oxide fluxes were measured daily for 35 d. Soil O2, temperature, and water content were continuously measured at multiple depths. Inorganic nitrogen, organic carbon, and soil pH were measured at 6‐d intervals. Measurements of denitrification enzyme activity with and without acetylene inhibition were used to infer the N2O/(N2O + N2) ratio. The N2O/(N2O + N2) ratio was lower under high‐ compared with low‐frequency irrigation, suggesting greater potential for N2O reduction to N2 with more frequent irrigation. Although N2O fluxes were increased by urine addition, they were not affected by irrigation frequency. Soil O2 decreased temporarily after urine deposition, but O2 dynamics did not explain N2O dynamics. Relative soil gas diffusivity (DP/DO) was a better predictor of N2O fluxes than O2 concentration. On a free‐draining soil, increasing irrigation frequency while providing the same total water volume did not enhance N2O emissions under ruminant urine patches in a grazed pasture.
Core Ideas
Irrigation effects on N2O emissions from ruminant urine patches are rarely studied.
Irrigation frequency influenced soil oxygen and N2O reductase enzyme.
N2O emission was unaffected by irrigation frequency on a free‐draining soil
Soil gas diffusivity (DP/DO) was a strong predictor of cumulative N2O emissions.
To identify prognostic factors associated with 90-day mortality in patients with oesophageal perforation (OP), and characterize the specific timeline from presentation to intervention, and its ...relation to mortality.
OP is a rare gastro-intestinal surgical emergency with a high mortality rate. However, there is no updated evidence on its outcomes in the context of centralized esophago-gastric services; updated consensus guidelines; and novel non-surgical treatment strategies.
A multi-center, prospective cohort study involving eight high-volume esophago-gastric centers (January 2016 to December 2020) was undertaken. The primary outcome measure was 90-day mortality. Secondary measures included length of hospital and ICU stay, and complications requiring re-intervention or re-admission. Mortality model training was performed using random forest, support-vector machines, and logistic regression with and without elastic net regularisation. Chronological analysis was performed by examining each patient's journey timepoint with reference to symptom onset.
The mortality rate for 369 patients included was 18.9%. Patients treated conservatively, endoscopically, surgically, or combined approaches had mortality rates of 24.1%, 23.7%, 8.7%, and 18.2%, respectively. The predictive variables for mortality were Charlson comorbidity index, haemoglobin count, leucocyte count, creatinine levels, cause of perforation, presence of cancer, hospital transfer, CT findings, whether a contrast swallow was performed, and intervention type. Stepwise interval model showed that time to diagnosis was the most significant contributor to mortality.
Non-surgical strategies have better outcomes and may be preferred in selected cohorts to manage perforations. Outcomes can be significantly improved through better risk-stratification based on afore-mentioned modifiable risk factors.
The rich ecology of tropical forests is intimately tied to their moisture status. Multi-site syntheses can provide a macro-scale view of these linkages and their susceptibility to changing climates. ...Here, we report pan-tropical and regional-scale analyses of tree vulnerability to drought. We assembled available data on tropical forest tree stem mortality before, during, and after recent drought events, from 119 monitoring plots in 10 countries concentrated in Amazonia and Borneo. In most sites, larger trees are disproportionately at risk. At least within Amazonia, low wood density trees are also at greater risk of drought-associated mortality, independent of size. For comparable drought intensities, trees in Borneo are more vulnerable than trees in the Amazon. There is some evidence for lagged impacts of drought, with mortality rates remaining elevated 2 yr after the meteorological event is over. These findings indicate that repeated droughts would shift the functional composition of tropical forests toward smaller, denser-wooded trees. At very high drought intensities, the linear relationship between tree mortality and moisture stress apparently breaks down, suggesting the existence of moisture stress thresholds beyond which some tropical forests would suffer catastrophic tree mortality.
Approximately 20% of people experience chronic pain after total knee replacement, but effective treatments are not available. We aimed to evaluate the clinical effectiveness and cost-effectiveness of ...a new care pathway for chronic pain after total knee replacement.
We did an unmasked, parallel group, pragmatic, superiority, randomised, controlled trial at eight UK National Health Service (NHS) hospitals. People with chronic pain at 3 months after total knee replacement surgery were randomly assigned (2:1) to the Support and Treatment After Replacement (STAR) care pathway plus usual care, or to usual care alone. The STAR intervention aimed to identify underlying causes of chronic pain and enable onward referrals for targeted treatment through a 3-month post-surgery assessment with an extended scope practitioner and telephone follow-up over 12 months. Co-primary outcomes were self-reported pain severity and pain interference in the replaced knee, assessed with the Brief Pain Inventory (BPI) pain severity and interference scales at 12 months (scored 0–10, best to worst) and analysed on an as-randomised basis. Resource use, collected from electronic hospital records and participants, was valued with UK reference costs. Quality-adjusted life-years (QALYs) were calculated from EQ-5D-5L responses. This trial is registered with ISRCTN, ISRCTN92545361.
Between Sept 6, 2016, and May 31, 2019, 363 participants were randomly assigned to receive the intervention plus usual care (n=242) or to receive usual care alone (n=121). Participants had a median age of 67 years (IQR 61 to 73), 217 (60%) of 363 were female, and 335 (92%) were White. 313 (86%) patients provided follow-up data at 12 months after randomisation (213 assigned to the intervention plus usual care and 100 assigned to usual care alone). At 12 months, the mean between-group difference in the BPI severity score was −0·65 (95% CI −1·17 to −0·13; p=0·014) and the mean between-group difference in the BPI interference score was −0·68 (−1·29 to −0·08; p=0·026), both favouring the intervention. From an NHS and personal social services perspective, the intervention was cost-effective (greater improvement with lower cost), with an incremental net monetary benefit of £1256 (95% CI 164 to 2348) at £20 000 per QALY threshold. One adverse reaction of participant distress was reported in the intervention group.
STAR is a clinically effective and cost-effective intervention to improve pain outcomes over 1 year for people with chronic pain at 3 months after total knee replacement surgery.
National Institute for Health Research.
The Amazon rain forest sustains the world's highest tree diversity, but it remains unclear why some clades of trees are hyperdiverse, whereas others are not. Using dated phylogenies, estimates of ...current species richness and trait and demographic data from a large network of forest plots, we show that fast demographic traits – short turnover times – are associated with high diversification rates across 51 clades of canopy trees. This relationship is robust to assuming that diversification rates are either constant or decline over time, and occurs in a wide range of Neotropical tree lineages. This finding reveals the crucial role of intrinsic, ecological variation among clades for understanding the origin of the remarkable diversity of Amazonian trees and forests.
To establish the relative success of treatment by unstimulated in vitro maturation (IVM) of oocytes or stimulated in vitro fertilization (IVF) in women with polycystic ovaries undergoing assisted ...conception treatment.
The case-control study included 107 IVM and 107 IVF cycles matched for age and cause of infertility. In vitro maturation patients underwent transvaginal recovery of immature oocytes during an unstimulated cycle, in vitro oocyte maturation, and fertilization. Those in the IVF group underwent ovarian stimulation after pituitary suppression. Embryos were transferred in the same cycle in both groups. Main outcome measures included numbers of mature oocytes and embryos produced, and rates of implantation, pregnancy, live birth, and complications.
In the IVM group after in vitro culture, 7.8 mature oocytes and 6.1 embryos were obtained per retrieval. With IVF, 12.0 mature oocytes (P <.01) and 9.3 embryos (P <.01) were obtained. The IVM pregnancy and live birth rates per retrieval were 26.2% and 15.9% compared with 38.3% and 26.2% for IVF (nonsignificant). The implantation rate of IVF-derived embryos was higher (17.1% versus 9.5%) than that for IVM (P <.01). There were 12 cases (11.2%) of moderate or severe ovarian hyperstimulation syndrome in IVF patients, compared with none in the IVM group (P <.01).
Our results suggest that for women with polycystic ovaries who require assisted conception, IVM is a promising alternative to conventional IVF treatment.
To assess the hypotheses that compound leaves of trees in the Amazon forest are an adaptation to drought and/or rapid growth. Amazon rain forest, South America. Genera from 137 permanent forest plots ...spread across Amazonia were classified into those with compound leaves and those with simple leaves. Metrics of compound leaf prevalence were then calculated for each plot and regression models that accounted for spatial autocorrelation were used to identify associations between climate variables and compound leaf structure. We also tested for associations between compound leaf structure and a variety of ecological variables related to life history and growth strategies, including wood density, annual increase in diameter and maximum height. One plant family, Fabaceae, accounts for 53% of compound-leaved individuals in the dataset, and has a geographical distribution strongly centred on north-east Amazonia. On exclusion of Fabaceae from the analysis we found no significant support for the seasonal drought hypothesis. However, we found evidence supporting the rapid growth hypothesis, with possession of compound leaves being associated with faster diameter growth rates and lower wood densities. This study provides evidence that possession of compound leaves constitutes one of a suite of traits and life-history strategies that promote rapid growth in rain forest trees. Our findings highlight the importance of carefully considering the geographical distribution of dominant taxa and spatial clustering of data points when inferring ecological causation from environment-trait associations.
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