From the Glovebox to the Benchtop: Air-Stable High Performance Molybdenum Alkylidyne Catalysts for Alkyne Metathesis.

Molybdenum alkylidynes endowed with tripodal silanolate ligands belong to the most active and selective catalysts for alkyne metathesis known to date. This paper describes a new generation that is distinguished by an unprecedented level of stability and practicality without sacrificing the chemical virtues of their predecessors. Specifically, pyridine adducts of type 16 are easy to make on gram scale, can be routinely weighed and handled in air, and stay intact for many months outside the glovebox. When dissolved in toluene, however, spontaneous dissociation of the stabilizing pyridine ligand releases an active species of excellent performance and functional group tolerance. Specifically, a host of polar and apolar groups, various protic sites, and numerous basic functionalities proved compatible. The catalysts are characterized by crystallographic and spectroscopic means, including 95Mo NMR; their activity and stability are benchmarked in detail, and the enabling properties are illustrated by advanced applications to natural product synthesis. For the favorable overall application profile and ease of handling, complexes of this new series are expected to replace earlier catalyst generations and help encourage a more regular use of alkyne metathesis in general.

Pan-Arctic soil moisture control on tundra carbon sequestration and plant productivity.

Long-term atmospheric CO2 concentration records have suggested a reduction in the positive effect of warming on high-latitude carbon uptake since the 1990s. A variety of mechanisms have been proposed to explain the reduced net carbon sink of northern ecosystems with increased air temperature, including water stress on vegetation and increased respiration over recent decades. However, the lack of consistent long-term carbon flux and in situ soil moisture data has severely limited our ability to identify the mechanisms responsible for the recent reduced carbon sink strength. In this study, we used a record of nearly 100 site-years of eddy covariance data from 11 continuous permafrost tundra sites distributed across the circumpolar Arctic to test the temperature (expressed as growing degree days, GDD) responses of gross primary production (GPP), net ecosystem exchange (NEE), and ecosystem respiration (ER) at different periods of the summer (early, peak, and late summer) including dominant tundra vegetation classes (graminoids and mosses, and shrubs). We further tested GPP, NEE, and ER relationships with soil moisture and vapor pressure deficit to identify potential moisture limitations on plant productivity and net carbon exchange. Our results show a decrease in GPP with rising GDD during the peak summer (July) for both vegetation classes, and a significant relationship between the peak summer GPP and soil moisture after statistically controlling for GDD in a partial correlation analysis. These results suggest that tundra ecosystems might not benefit from increased temperature as much as suggested by several terrestrial biosphere models, if decreased soil moisture limits the peak summer plant productivity, reducing the ability of these ecosystems to sequester carbon during the summer.

"Canopy Catalysts" for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal Ligand Framework.

A new family of structurally well-defined molybdenum alkylidyne catalysts for alkyne metathesis, which is distinguished by a tripodal trisilanolate ligand architecture, is presented. Complexes of type 1 combine the virtues of previous generations of silanolate-based catalysts with a significantly improved functional group tolerance. They are easy to prepare on scale; the modularity of the ligand synthesis allows the steric and electronic properties to be fine-tuned and hence the application profile of the catalysts to be optimized. This opportunity is manifested in the development of catalyst 1f, which is as reactive as the best ancestors but exhibits an unrivaled scope. The new catalysts work well in the presence of unprotected alcohols and various other protic groups. The chelate effect entails even a certain stability toward water, which marks a big leap forward in metal alkylidyne chemistry in general. At the same time, they tolerate many donor sites, including basic nitrogen and numerous heterocycles. This aspect is substantiated by applications to polyfunctional (natural) products. A combined spectroscopic, crystallographic, and computational study provides insights into structure and electronic character of complexes of type 1. Particularly informative are a density functional theory (DFT)-based chemical shift tensor analysis of the alkylidyne carbon atom and 95Mo NMR spectroscopy; this analytical tool had been rarely used in organometallic chemistry before but turns out to be a sensitive probe that deserves more attention. The data show that the podand ligands render a Mo-alkylidyne a priori more electrophilic than analogous monodentate triarylsilanols; proper ligand tuning, however, allows the Lewis acidity as well as the steric demand about the central atom to be adjusted to the point that excellent performance of the catalyst is ensured.

Metathesis at an Implausible Site: A Formal Total Synthesis of Rhizoxin†D.

The new approach to the anticancer agent rhizoxin D described herein does not cohere with the conventional logic of metathesis, according to which macrocycles are best closed at a disubstituted olefinic site; rather, the trisubstituted C11-C12 alkene flanked by an allylic -OH group served as the pivot point for synthesis. This motif was attained in good yield and excellent selectivity by a sequence of alkyne metathesis, trans-hydrostannation and cross coupling. Because the exact same substructure is prominently featured in numerous other natural products, the underpinning strategy, though unusual, might bear more general relevance.

Long-term follow-up of motor cortex stimulation for neuropathic pain in 23 patients.

BACKGROUND: Motor cortex stimulation (MCS) is being offered to patients suffering from neuropathic pain. Outcome prediction, programming and especially sustaining a long-term treatment effect represent major challenges. We report a retrospective long-term analysis of our patients treated with MCS over a median follow-up of 39.1 months. OBJECTIVES: To investigate the time course of the treatment effect in MCS for neuropathic pain. METHODS: Twenty-three closely followed patients treated with MCS were retrospectively analyzed. Reduction in pain measured on a visual analogue scale (VAS) was defined as the primary outcome parameter. VAS pain level and adverse events were documented at the 1-, 3-, 6-, 12-, 18- and 24-month follow-ups. RESULTS: The mean VAS under best medical treatment was 7.8 (SD 1.2, range 5-9) with escalation to 9.3 (SD 0.9, range 6-10) when the patients' medications were missed or delayed. About half of the patients (47.8%) experienced a satisfactory (>50%) reduction in pain during the first month of treatment. The best treatment results were seen at the 3-month follow-up (mean VAS 4.8, SD 1.9, -37.2% compared to baseline). A decline in the treatment effect was generally observed at the subsequent follow-up assessments. Six patients had their devices explanted during the follow-up period due to loss of treatment effect. CONCLUSIONS: In this study, MCS failed to provide long-term pain control for neuropathic pain. Many aspects of MCS still remain unclear, especially the neural circuits involved and their response to long-term stimulation. Means must be developed to overcome the problems in this promising technique.

Coordination chemistry of cyclopropenylidene-stabilized phosphenium cations: synthesis and reactivity of Pd and Pt complexes.

A straightforward synthesis of cyclopropenylidene-stabilized phosphenium cations 1 a-g through the reaction of [(iPr2N)2C3(+)Cl]BF4 with secondary phosphines is described. Their donor ability was evaluated by analysis of the CO stretching frequency in Rh complexes [RhCl(CO)L2](BF4)2 and electrochemical methods. The cyclopropenium ring induces a phosphite-type behavior that can be tuned by the other two substituents attached to the phosphorus atom. Despite of the positive charge that they bear, phosphenium cations 1 a-g still act as two-electron donor ligands, forming adducts with Pd(II) and Pt(II) precursors. Conversely, in the presence of Pd(0) species, an oxidative insertion of the Pd atom into the Ccarbene-phosphorus bond takes place, providing dimeric structures in which each Pd atom is bonded to a cyclopropenyl carbene while two dialkyl/diaryl phosphide ligands serve as bridges between the two Pd centers. The catalytic performance of the resulting library of Pt(II) complexes was tested; all of the cationic phosphines accelerated the prototype 6-endo-dig cyclization of 2-ethynyl-1,1'-biphenyl to afford pentahelicene. The best ligand 1 g was used in the synthesis of two natural products, chrysotoxene and epimedoicarisoside A.

Continuous perioperative apomorphine in deep brain stimulation surgery for Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease (PD) deprived of dopaminergic medication to facilitate awake testing during the deep brain stimulation (DBS) procedure are at increased risk of neurologic deterioration.. The aim of this survey was to demonstrate the safety of subcutaneous apomorphine treatment for reducing surgery-related neurologic deterioration in patients undergoing DBS surgery for PD. METHODS: Ninety-two patients who underwent DBS surgery for PD between 11/2007 and 10/2011 in our department were retrospectively analyzed for this survey. Demographic data, apomorphine dosage, side-effects and need of ICU/IMC stay were collected and analyzed. RESULTS: Seventy-two out of 92 patients (78.3%) received apomorphine treatment; main reason for omission of treatment was intolerable nausea (16/92, 17.3%). Apomorphine treatment was well tolerated and the most common side effect was nodular panniculitis. No severe complications were observed. No patient required ICU/IMC stay related to dopaminergic deprivation. CONCLUSIONS: Perioperative withdrawal of dopaminergic medication in PD patients leads to an increased risk of neurologic and respiratory deterioration during DBS procedures. These complications can likely be tempered using perioperative subcutaneous apomorphine as a substitute. Our 5-year experience indicates a reduction in postoperative neurologic deterioration and ICU/IMC stay need. We consider perioperative apomorphine safe during DBS surgery for PD.

Synthesis, structure, and applications of pyridiniophosphines.

A new family of cationic ligands, N-alkyl/aryl pyridiniophosphines, has been synthesized through a short, scalable, and highly modular route. Evaluation of their electronic properties evidenced weak σ-donor and quite strong π-acceptor character when used as ancillary ligands. These attributes confer a substantially enhanced π-acidity to the Pt(II) and Au(I) complexes thereof derived and, as result, they depict an improved ability to activate alkynes towards nucleophilic attack. This superior performance has been demonstrated along several mechanistically diverse Pt(II)- and Au(I)-catalyzed transformations.

Predicting outcome in peripheral nerve stimulation for chronic neuropathic pain.

OBJECTIVE: The aim of the study was to investigate the predictive value of percutaneous electrical nerve stimulation (PENS) in peripheral nerve stimulation (PNS) for chronic neuropathic pain. MATERIALS AND METHODS: Twelve patients being evaluated for PNS for chronic neuropathic pain were included in this survey. Stimulation with acupuncture needles was applied with continuous high frequency stimulation. Position, polarity, frequency and amperage threshold of perception, and adverse effects were noted. Additional stimulation side effects were documented. A StimScore was developed to evaluate effects in a standardized manner. This StimScore comprises coverage of the painful area, therapeutic range, and amperage required for successful stimulation. StimScore was determined during PENS, during test stimulation, and under final stimulation. RESULTS: PNS was well tolerated by all patients. Seven of the 12 patients (58%) were classified as successfully treated, and 5/12 patients (42%) as unsuccessful. The mean overall pain reduction in the first group was 4.0 points (SD = 2.87, P = 0.010) and 2.4 points (SD = 1.29, P = 0.014), respectively, on the visual analogue scale. In the successful stimulation group, a mean StimScore of 13.14 (SD 11.19-15.0) was calculated vs. 10.4 (95% CI 8.52-12.28) in the unsuccessful stimulation group (P = 0.033, 95% CI = 0.265-5.220). CONCLUSIONS: Predicting response to PNS is crucial to reduce the number of patients implanted in vain. To adopt PENS via electroacupuncture needles as a percutaneous simulation method for PNS seemed to be feasible. The technique presented herein bears the potential to improve patient selection combined with reduced invasiveness. The presented results are encouraging and deliver a starting point for further trials.

Alternative Dorsal Root Ganglion Neuromodulation Electrode Implantation: A Report of 2 Cases with 3 Different Techniques.

BACKGROUND AND STUDY AIMS: The traditional percutaneous placement of dorsal root ganglion (DRG) electrodes may not be eligible for every patient. In this tertiary spine surgery and interventional pain therapy center, alternative neurostimulation implantation techniques were developed and applied where standard percutaneous approaches failed or were contraindicated. CASE PRESENTATION: Three alternative implantation techniques can be used: (1) open surgical placement of DRG leads, (2) two-lead insertion via a lateral to medial transforaminal approach (level L3), and (3) percutaneous approach with two leads close to the spinal nerves L4 (peripheral nerve stimulation). RESULTS: The placement of the leads occurred without complications and resulted in similar expected outcomes as with the common percutaneous technique with long-term stable pain suppression at 7 months and 1 year. CONCLUSIONS: In patients in whom the DRG cannot be approached by the standard percutaneous approach, at least three alternatives may be used in experienced hands resulting in stable pain suppression of similar magnitude.

Long-term effects of rewetting and drought on GPP in a temperate peatland based on satellite remote sensing data.

Rewetting previously drained peatlands restores the critical function of peatlands as long-term carbon storages and sinks currently threatened by climate change and additional human-induced disturbances. Understanding and projecting the restoration process by rewetting, however, currently face a pressing challenge, the lack of consistent and gap-free records of important carbon cycling indicators of peatlands such as the gross primary production (GPP) over long term. In this study, we reconstructed the GPP in a rewetted peatland called Zarnekow (Fluxnet-ID: DE-Zrk) in Germany from 2000 to 2020 by combining long-term satellite observations and limited-term tower-based eddy covariance (EC) measurements based on Random Forest regression models. The R2 between the reconstructed data and EC data was 0.6. The reasonable reconstruction of long-term GPP enabled trend analysis that identified two distinct periods of decreasing/increasing in GPP due to rewetting and droughts. Rewetting in the winter of 2004 and 2005 stabilized GPP after a decreasing period. A drought in 2018 significantly increased GPP, and GPP remained high over the following two years. Furthermore, the month-specific trends show significant seasonality at this site, specifically, an increasing trend over the 21 years in the growing-season months of June to August and a decreasing trend in the other months. The most important variables for satellite-based estimates of GPP at this site include total evapotranspiration, land surface temperature, enhanced vegetation index and near-infrared reflectance vegetation index. Long-term analyses of carbon fluxes through the combination of satellite observations and EC measurements provide crucial insights into the restoration of carbon sequestration functions in rewetted peatlands.

Monitoring of carbon-water fluxes at Eurasian meteorological stations using random forest and remote sensing.

Simulating the carbon-water fluxes at more widely distributed meteorological stations based on the sparsely and unevenly distributed eddy covariance flux stations is needed to accurately understand the carbon-water cycle of terrestrial ecosystems. We established a new framework consisting of machine learning, determination coefficient (R2), Euclidean distance, and remote sensing (RS), to simulate the daily net ecosystem carbon dioxide exchange (NEE) and water flux (WF) of the Eurasian meteorological stations using a random forest model or/and RS. The daily NEE and WF datasets with RS-based information (NEE-RS and WF-RS) for 3774 and 4427 meteorological stations during 2002-2020 were produced, respectively. And the daily NEE and WF datasets without RS-based information (NEE-WRS and WF-WRS) for 4667 and 6763 meteorological stations during 1983-2018 were generated, respectively. For each meteorological station, the carbon-water fluxes meet accuracy requirements and have quasi-observational properties. These four carbon-water flux datasets have great potential to improve the assessments of the ecosystem carbon-water dynamics.

Percutaneous implanted paddle lead for spinal cord stimulation: technical considerations and long-term follow-up.

OBJECTIVES: Spinal cord stimulation (SCS) is an established method for treatment of chronic pain. Cylindrical-type leads can be implanted percutaneously. In contrast, paddle leads (lamitrode) require more invasive surgery (i.e., laminotomy or laminectomy) for placement into the epidural space, thereby offering several advantages over percutaneous leads (octrode), including less lead migration and better paresthesia coverage. The goal of this study was to prospectively demonstrate the safety and efficacy of a percutaneous paddle lead for SCS. MATERIALS AND METHODS: This prospective trial enrolled 81 patients. The mean age was 57 years (range 27-82 years) with an almost equal sex distribution (male 47%, female 53%). Most patients (90%) had failed back surgery syndrome combined with lower extremity pain and lower back pain. A percutaneous paddle lead was implanted using a novel introduction system for percutaneous implantation. All implantations were performed under local anesthesia. Prior to the final implantation of the impulse generator, all patients underwent seven days of trial stimulation with pain assessment using a visual analog scale (VAS). The median follow-up was 12 months. RESULTS: The data showed favorable clinical outcomes for paresthesia coverage and pain reduction (median VAS 8.4 vs. 2.3), with a risk profile comparable with known percutaneous techniques. Compared with the published data (2-22%), the lead migration rate in this study was low (2.5%). No perioperative complications occurred. CONCLUSIONS: This new, minimally invasive percutaneous paddle lead is effective and safe, with a low migration rate. Placement can be done under local anesthesia, allowing an intraoperative assessment of the paresthesia coverage in terms of pain relief. This approach is less invasive and offers a faster and more comfortable procedure compared with laminotomy or laminectomy.

Earlier snowmelt may lead to late season declines in plant productivity and carbon sequestration in Arctic tundra ecosystems.

Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season.

Vegetation type is an important predictor of the arctic summer land surface energy budget.

Despite the importance of high-latitude surface energy budgets (SEBs) for land-climate interactions in the rapidly changing Arctic, uncertainties in their prediction persist. Here, we harmonize SEB observations across a network of vegetated and glaciated sites at circumpolar scale (1994-2021). Our variance-partitioning analysis identifies vegetation type as an important predictor for SEB-components during Arctic summer (June-August), compared to other SEB-drivers including climate, latitude and permafrost characteristics. Differences among vegetation types can be of similar magnitude as between vegetation and glacier surfaces and are especially high for summer sensible and latent heat fluxes. The timing of SEB-flux summer-regimes (when daily mean values exceed 0 Wm-2) relative to snow-free and -onset dates varies substantially depending on vegetation type, implying vegetation controls on snow-cover and SEB-flux seasonality. Our results indicate complex shifts in surface energy fluxes with land-cover transitions and a lengthening summer season, and highlight the potential for improving future Earth system models via a refined representation of Arctic vegetation types.

Chronic high-frequency deep-brain stimulation in progressive myoclonic epilepsy in adulthood--report of five cases.

PURPOSE: To assess the efficacy and tolerability of chronic high-frequency deep brain stimulation (DBS) in adult patients with progressive myoclonic epilepsy (PME) syndromes. METHODS: Five adult patients (four male, 28-39 years) with PME underwent chronic high-frequency DBS according to a study protocol that had been approved by the local ethics committee. Electrodes were implanted in the substantia nigra pars reticulata (SNr)/subthalamic nucleus (STN) region in the first patient and additionally in the ventral intermediate nucleus (VIM) bilaterally in the following four cases. Follow-up took place in intervals of 3 months and DBS effects were compared with baseline frequency of passive and activation-induced myoclonic jerks and daily life performance 8 weeks prior to implantation. KEY FINDINGS: Follow-up periods ranged from 12-42 months (median 24 months). The best clinical effects were seen with SNr/STN DBS in all patients. VIM stimulation failed to achieve acute therapeutic effects and revealed low side-effect thresholds and even triggering of myoclonia. In all patients the reduction of myoclonic seizures was observed and ranged between 30% and 100% as quantified by a standardized video protocol. All patients reported clinically relevant improvements of various capabilities such as free standing and walking or improved fine motor skills. In one patient with an excellent initial response generalized tonic-clonic seizures increased after 3 months of stimulation following extensive trauma-related surgery. The best effect was seen in the least impaired patient. SIGNIFICANCE: DBS of the SNr/STN may be an effective treatment option for patients with PME. Less impaired patients may benefit more markedly.

The impact of occasional drought periods on vegetation spread and greenhouse gas exchange in rewetted fens.

Peatland rewetting aims at stopping the emissions of carbon dioxide (CO2) and establishing net carbon sinks. However, in times of global warming, restoration projects must increasingly deal with extreme events such as drought periods. Here, we evaluate the effect of the European summer drought 2018 on vegetation development and the exchange of methane (CH4) and CO2 in two rewetted minerotrophic fens (Hütelmoor-Hte and Zarnekow-Zrk) including potential carry-over effects in the post-drought year. Drought was a major stress factor for the established vegetation but also promoted the rapid spread of new vegetation, which will likely gain a lasting foothold in Zrk. Accordingly, drought increased not only respiratory CO2 losses but also photosynthetic CO2 uptake. Altogether, the drought reduced the net CO2 sink in Hte, while it stopped the persistent net CO2 emissions of Zrk. In addition, the drought reduced CH4 emissions in both fens, though this became most apparent in the post-drought year and suggests a lasting shift towards non-methanogenic organic matter decomposition. Occasional droughts can be beneficial for the restoration of the peatland carbon sink function if the newly grown vegetation increases CO2 sequestration in the long term. Nonetheless, care must be taken to prevent extensive peat decay. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.

Paddle versus cylindrical leads for percutaneous implantation in spinal cord stimulation for failed back surgery syndrome: a single-center trial.

OBJECTIVE: Spinal cord stimulation is an interventional treatment for chronic pain syndromes such as failed back surgery syndrome (FBSS), and it utilizes either cylindrical or paddle electrodes placed percutaneously into the epidural space. This prospective nonrandomized single-center study investigated the specific advantages and disadvantages of percutaneously implanted paddle and cylindrical leads in patients with FBSS. METHODS: Over a 2-year period, 100 patients with FBSS (43 men; 57 women; mean age: 56.3 years) were included. Paddle leads were placed percutaneously under local anesthesia in 50 patients; conventional percutaneous cylindrical lead implantation was performed in the other 50 patients (one lead permitted per patient). Follow-up included the Visual Analog Scale (VAS) assessment of pain and administration of the Oswestry Disability Questionnaire. RESULTS: Similar significant pain reduction (69%) was demonstrated in both groups (VAS pre/post: paddle: 8.8/3.7; cylindrical: 8.5/3.8). Using the same perioperative protocol for each group, we observed higher dislocation and infection rates for the cylindrical group (14% and 10%, respectively) than for the paddle group (6% and 2%, respectively). CONCLUSION: Minimally invasive percutaneous paddle and cylindrical leads are safe and effective, have low complication rates, and perform well in patients with FBSS. Both devices can be implanted using a local anesthetic, so that intraoperative and reproducible testing stimulation can be performed for sufficient paresthesia overlap prior to permanent device fixation.

Hydrology-driven ecosystem respiration determines the carbon balance of a boreal peatland.

The carbon (C) balance of boreal peatlands is mainly the sum of three different C fluxes: carbon dioxide (CO2), methane (CH4) and dissolved organic carbon (DOC). Intra- and inter-annual dynamics of these fluxes are differentially controlled by similar factors, such as temperature and water-table. Different climatic conditions within and between years might thus result in varying absolute and relative contributions of each flux to net ecosystem productivity (NEP). In this study CO2 fluxes were measured at a boreal peatland in eastern Finland during a dry year (2006) and a wet year (2007) and combined with DOC and CH4 fluxes from the same site. CO2 uptake in the wet year was 65% higher than in the dry year, caused by higher water table (WT) and subsequently reduced rates of soil respiration. Two to three-fold increases in DOC and CH4 fluxes in the wet year did not completely offset the higher CO2 uptake in that year, resulting in NEP of -83.7±14 g C m(-2) in the dry and -134.5±21 g C m(-2) in the wet year. Thus, in our study, WT was identified as the most important factor responsible for variations in the C balance between the observed years.