Minimizing habitat conflicts in meeting net-zero energy targets in the western United States.

The scale and pace of energy infrastructure development required to achieve net-zero greenhouse gas (GHG) emissions are unprecedented, yet our understanding of how to minimize its potential impacts on land and ocean use and natural resources is inadequate. Using high-resolution energy and land-use modeling, we developed spatially explicit scenarios for reaching an economy-wide net-zero GHG target in the western United States by 2050. We found that among net-zero policy cases that vary the rate of transportation and building electrification and use of fossil fuels, nuclear generation, and biomass, the "High Electrification" case, which utilizes electricity generation the most efficiently, had the lowest total land and ocean area requirements (84,000 to 105,000 km2 vs. 88,100 to 158,000 km2 across all other cases). Different levels of land and ocean use protections were applied to determine their effect on siting, environmental and social impacts, and energy costs. Meeting the net-zero target with stronger land and ocean use protections did not significantly alter the share of different energy generation technologies and only increased system costs by 3%, but decreased additional interstate transmission capacity by 20%. Yet, failure to avoid development in areas with high conservation value is likely to result in substantial habitat loss.

Persistent Disparities in Access to Elective Colorectal Cancer Surgery After Medicaid Expansion Under the Affordable Care Act: A Multistate Evaluation.

BACKGROUND: Despite their higher incidence of colorectal cancer, ethnoracial minority and low-income patients have reduced access to elective colorectal cancer surgery. Although the Affordable Care Act's Medicaid expansion increased screening of colonoscopies, its effect on disparities in elective colorectal cancer surgery remains unknown. OBJECTIVE: This study assessed the effects of Medicaid expansion on elective colorectal cancer surgery rates overall and by race-ethnicity and income. DESIGN: Using the 2012 to 2015 State Inpatient Databases, a retrospective cohort study was conducted. SETTINGS: State Inpatient Databases from 3 expansion states (Maryland, New Jersey, and Kentucky) and 2 nonexpansion states (Florida and North Carolina) were used. PATIENTS: This study examined 22,304 adult patients aged 18 to 64 years who underwent colorectal cancer surgery. MAIN OUTCOME MEASURES: Using interrupted time series analysis, the effect of Medicaid expansion on the odds of elective colorectal cancer surgery was assessed. RESULTS: Elective vs nonelective surgery rates remained unchanged overall (70.2% vs 70.7%, p = 0.63) and in ethnoracial minorities in expansion states (whites from 72.8% to 73.8% pre to post, p = 0.40 and non-white from 64.0% to 63.1% pre to post, p = 0.67). There was an instantaneous increase in odds of elective surgery in expansion vs nonexpansion states at policy implementation (adjusted OR 1.37; 95% CI, 1.05-1.79; p = 0.02), but it subsequently decreased (combined adjusted OR 0.95; 95% CI, 0.92-0.99; p = 0.03). Elective surgery rates were also unchanged among ethnoracial minorities (instantaneous changes in expansion states, combined effect 1.06; pre-trend 1.01 vs post-trend 0.98) and low-income persons in expansion states (pre-trend 1.03 vs post-trend 0.97) (for all, p > 0.1). LIMITATIONS: The study was limited to 5 states. Although patients may have increased access to cancer screening services and surgery after expansion, the State Inpatient Databases only provide information on patients who underwent surgery. CONCLUSIONS: Despite gains in screening, Medicaid expansion was not associated with reductions in known ethnoracial or income-based disparities in elective colorectal cancer surgery rates. Expanding access to colorectal cancer surgery for underserved populations likely requires attention to provider and health system factors contributing to persistent disparities. See Video Abstract at http://links.lww.com/DCR/C217 . DISPARIDADES PERSISTENTES EN EL ACCESO A LA CIRUGA ELECTIVA DEL CNCER COLORRECTAL DESPUS DE LA EXPANSIN DE MEDICAID EN VIRTUD DE LA LEY DEL CUIDADO DE SALUD A BAJO PRECIO UNA EVALUACIN MULTIESTATAL: ANTECEDENTES: A pesar de su mayor incidencia de cáncer colorrectal, los pacientes de minorías etnoraciales y de bajos ingresos tienen un acceso reducido a la cirugía electiva de cáncer colorrectal. Aunque la expansión de Medicaid de la Ley del Cuidado de Salud a Bajo Precio aumentó las colonoscopias de detección, aún se desconoce su efecto sobre las disparidades en la cirugía electiva de cáncer colorrectal.OBJETIVO: Este estudio evaluó los efectos de la expansión de Medicaid en las tasas de cirugía electiva de cáncer colorrectal en general y por raza, etnia e ingresos.DISEÑO: Utilizando las bases de datos estatales de pacientes hospitalizados de 2012-2015, se realizó un estudio de cohorte retrospectivo.CONFIGURACIÓN: Se utilizaron bases de datos estatales de pacientes hospitalizados de tres estados en expansión (Maryland, Nueva Jersey, Kentucky) y dos estados sin expansión (Florida, Carolina del Norte).PACIENTES: Este estudio examinó a 22,304 pacientes adultos de 18 a 64 años que se sometieron a cirugía de cáncer colorrectal.RESULTADO PRINCIPAL: Mediante el análisis de series de tiempo interrumpido, se evaluó el efecto de la expansión de Medicaid en las probabilidades de cirugía electiva de cáncer colorrectal.RESULTADOS: Las tasas de cirugía electiva frente a no electiva permanecieron sin cambios en general (70,2% frente a 70,7%, p = 0,63) y en las minorías etnoraciales en los estados de expansión (blancos del 72,8% al 73,8 % antes y después, p = 0,40 y no blancos del 64,0% al 63,1% pre a post, p = 0,67). Hubo un aumento instantáneo en las probabilidades de cirugía electiva en los estados de expansión frente a los de no expansión en la implementación de la política (OR ajustado 1,37, IC del 95%, 1,05-1,79, p = 0,02), pero disminuyó posteriormente (OR ajustado combinado 0,95, 95% IC, 0,92-0,99, p = 0,03). Las tasas de cirugía electiva también se mantuvieron sin cambios entre las minorías etnoraciales (cambios instantáneos en los estados de expansión, efecto combinado 1,06; antes de la tendencia 1,01 frente a la postendencia 0,98) y las personas de bajos ingresos en los estados de expansión (antes de la tendencia 1,03 frente a la postendencia 0,97; para todos, p > 0,1).LIMITACIONES: El estudio se limitó a cinco estados. Si bien los pacientes pueden tener un mayor acceso a los servicios de detección de cáncer y la expansión posterior a la cirugía, la base de datos de pacientes hospitalizados del estado solo brinda información sobre los pacientes que se sometieron a cirugía.CONCLUSIONES: A pesar de los avances en la detección, la expansión de Medicaid no se asoció con reducciones en las disparidades etnoraciales o basadas en los ingresos conocidas en las tasas de cirugía electiva de cáncer colorrectal. Ampliar el acceso a la cirugía del cáncer colorrectal para las poblaciones desatendidas probablemente requiera atención a los factores del proveedor y del sistema de salud que contribuyen a las disparidades persistentes. Consulte el Video Resumen en http://links.lww.com/DCR/C217 . (Traducción-Dr. Yesenia.Rojas-Khalil ).

Eclipse stemless shoulder prosthesis vs. Univers II shoulder prosthesis: a multicenter, prospective randomized controlled trial.

BACKGROUND: Total shoulder arthroplasty is an accepted treatment for glenohumeral osteoarthritis. The Arthrex Eclipse shoulder prosthesis is a stemless, canal-sparing humeral prosthesis with bone ingrowth capacity on the trunnion, as well as through the fenestrated hollow screw, that provides both diaphyseal and metaphyseal load sharing and fixation. METHODS: Between 2013 and 2018, 16 sites in the United States enrolled 327 patients (Eclipse in 237 and Arthrex Univers II in 90). All patients had glenohumeral arthritis refractory to nonsurgical care. Strict exclusion criteria were applied to avoid confounding factors such as severe patient comorbidities, arthritis not consistent with osteoarthritis, and medical or prior surgical treatments that may have affected outcomes. Patients were randomized to the Eclipse or Univers II group via block randomization. RESULTS: In total, 149 Eclipse and 76 Univers II patients reached 2-year follow-up (139 Eclipse patients [93.3%] and 68 Univers II patients [89.5%] had complete data). The success rate using the Composite Clinical Success score was 95% in the Eclipse group vs. 89.7% in the Univers II group. No patient exhibited radiographic evidence of substantial humeral radiolucency, humeral migration, or subsidence at any point. Reoperations were performed in 7 patients (3.2%) in the Eclipse group and 3 (3.8%) in the Univers II group. CONCLUSION: The Arthrex Eclipse shoulder prosthesis is a safe and effective humeral implant for patients with glenohumeral arthritis at 2-year follow-up, with no differences in outcomes compared with the Univers II shoulder prosthesis.

Tuberosity healing improves functional outcome following primary reverse shoulder arthroplasty for proximal humeral fractures with a 135° prosthesis.

INTRODUCTION: Reverse shoulder arthroplasty (RSA) is a common treatment for proximal humeral fractures (PHFs) in the elderly. This study evaluates the influence of tuberosity healing (TH) on functional outcome following a 135° humeral inclination RSA for PHFs. METHODS: Retrospectively, all patients with an acute PHF treated with a 135° humeral inclination RSA at four centers during a three-year period were followed up. Constant score (CS), TH and glenoid notching were analyzed. RESULTS: Sixty-four of 100 patients (64%) with a mean age of 76 ± 7 years were available for follow-up at 22 ± 8 months. The mean-adjusted CS was 72%. TH of the greater tuberosity (GT) was 77% and resulted in significantly improved forward flexion (128° vs. 92°; p = 0.003), external rotation (33° vs. 17°; p = 0.03) and adjusted CS (78% vs. 54%, p < 0.005). GT healing rate was 86% with neutral, 70% with lateralized and 33% with an inferior eccentric glenosphere. TH of the lesser tuberosity was 79%. There was 8% complication and 3% revision rate; implant survival was 100%. CONCLUSION: RSA with 135° humeral inclination for PHFs leads to good functional outcome, reproducible results and a high rate of TH. The short-term revision rate is low. TH is associated with improved ROM and functional outcome. LEVEL OF EVIDENCE: III.

Development of the Impact of Physical Activity Scale.

Despite evidence that exercise has physical and mental benefits, there is still a high dropout rate. One reason for why people struggle to maintain consistency in their workout programs is self-efficacy, the cognitive mechanism that predicts behavioral intention. Given that emotional arousal plays an important role in self-efficacy, we developed the Impact of Physical Activity (IPA) scale to investigate how positive and negative affect influence commitment to exercise. The findings demonstrate good internal reliability of the scale, as well as convergent and divergent validity with optimism and depression. The IPA also had good predictive validity of physical self-efficacy.

Adapting the bioblitz to meet conservation needs.

When conservation strategies require new, field-based information, practitioners must find the best ways to rapidly deliver high-quality survey data. To address this challenge, several rapid-assessment approaches have been developed since the early 1990s. These typically involve large areas, take many months to complete, and are not appropriate when conservation-relevant survey data are urgently needed for a specific locale. In contrast, bioblitzes are designed for quick collection of site-specific survey data. Although bioblitzes are commonly used to achieve educational or public-engagement goals, conservation practitioners are increasingly using a modified bioblitz approach to generate conservation-relevant data while simultaneously enhancing research capacity and building working partnerships focused on conservation concerns. We term these modified events expert bioblitzes. Several expert bioblitzes have taken place on lands of conservation concern in Southern California and have involved collaborative efforts of government agencies, nonprofit organizations, botanic gardens, museums, and universities. The results of expert bioblitzes directly informed on-the-ground conservation and decision-making; increased capacity for rapid deployment of expert bioblitzes in the future; and fostered collaboration and communication among taxonomically and institutionally diverse experts. As research and conservation funding becomes increasingly scarce, expert bioblitzes can play an increasingly important role in biodiversity conservation.

Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency.

BACKGROUND: Implantation of testosterone doses of at least 150 to 450 mg (ie, two to six pellets) is common clinical practice despite a lack of prospective data. AIM: To evaluate pharmacokinetics, clinical efficacy, safety, and patient-reported outcomes in men with androgen deficiency who received implantation of testosterone pellets (900 mg) in an open-label study. METHODS: Men with androgen deficiency (serum testosterone < 300 ng/dL [10.4 nmol/L]) were screened and received 12 testosterone pellets (900 mg). Serum hormone measurements (total and free testosterone, dihydrotestosterone, and estradiol) were obtained on days 1, 5, 8, 15, 29, 57, 85, and 113. All hormones were assayed using validated liquid chromatography and tandem mass spectrometry. OUTCOMES: Pharmacokinetics of selected hormones was determined. The patient-reported International Index of Erectile Function (IIEF), Center for Epidemiologic Studies Depression (CES-D), and Androgen Deficiency in the Aging Male (qADAM) questionnaires also were performed. Patients rated their satisfaction on a scale from 1 (very satisfied) to 5 (very dissatisfied). Adverse events were monitored throughout. RESULTS: Fifteen patients were included (mean age = 54.5 years, SD = 8.6 years). Mean baseline total testosterone concentration was 241.6 ng/dL (SD = 88.8 ng/dL; mean = 8.4 nmol/L, SD = 3.1 nmol/L). Mean testosterone serum concentrations fluctuated during the first 2 weeks (range = 300-1,000 ng/dL, 10.4-34.7 nmol/L) but remained higher than or equal to 300 ng/dL (10.4 nmol/L) through day 113. Concentrations of free testosterone, dihydrotestosterone, and estradiol mirrored that of total testosterone. Male functioning (IIEF score), depression (CES-D total score), and androgen-deficiency symptoms (qADAM total score) improved from baseline. Most patients were "very satisfied" (40.0%) or "quite satisfied" (26.7%) with treatment. Testosterone pellets were well tolerated. Pellet extrusion and polycythemia occurred in one patient each. CLINICAL IMPLICATIONS: Implantation of high doses (900 mg) of testosterone pellets are generally well tolerated and could provide clinical benefit for some patients. STRENGTHS AND LIMITATIONS: This study provides standardized data for the implantation of 12 testosterone pellets. However, the open-label uncontrolled design of this study and its small and ethnically non-diverse patient population limit the interpretation of these data, particularly the patient-reported outcomes. CONCLUSION: Implantation of 12 testosterone pellets (900 mg) was well tolerated and provided adequate and sustained serum testosterone concentrations. Additional randomized controlled trials are needed to confirm efficacy and safety findings. McMahon CG, Shusterman N, Cohen B. Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency. J Sex Med 2017;14:883-890.

Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial.

BACKGROUND: To determine the safety and efficacy of collagenase clostridium histolyticum (CCH) injection for the treatment of palmar Dupuytren disease nodules. METHODS: In this 8-week, double-blind trial, palpable palmar nodules on one hand of adults with Dupuytren disease were selected for treatment. Patients were randomly assigned using an interactive web response system to receive a dose of 0.25 mg, 0.40 mg, or 0.60 mg (1:1:1 ratio) and then allocated to active treatment (CCH) or placebo (4:1 ratio). All patients and investigators were blinded to treatment. One injection was made in the selected nodule on Day 1. Caliper measurements of nodule length and width were performed at screening and at Weeks 4 and 8. Investigator-reported nodular consistency and hardness were evaluated at baseline and Weeks 1, 4, and 8. Investigator-rated patient improvement (1 [very much improved] to 7 [very much worse]) and patient satisfaction were assessed at study end. RESULTS: In the efficacy population (n = 74), percentage changes in area were significantly greater with CCH 0.40 mg (-80.1%, P = 0.0002) and CCH 0.60 mg (-78.2%, P = 0.0003), but not CCH 0.25 mg (-58.3%, P = 0.079), versus placebo (-42.2%) at post-treatment Week 8. Mean change in nodular consistency and hardness were significantly improved with CCH versus placebo at Weeks 4 and 8 (P ≤ 0.0139 for all). At Week 8, investigator global assessment of improvement was significantly greater with CCH 0.40 mg and 0.60 mg (P ≤ 0.0014) but not statistically significant with CCH 0.25 mg versus placebo (P = 0.13). Most patients were "very satisfied" or "quite satisfied" with CCH 0.40 mg and 0.60 mg. Contusion/bruising (50.0% to 59.1%) was the most common adverse event with CCH treatment. CONCLUSION: In patients with Dupuytren disease, a single CCH injection significantly improved palmar nodule size and hardness. The safety of CCH was similar to that observed previously in patients with Dupuytren contracture. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02193828 . Date of trial registration: July 2, 2014 to December 5, 2014.

Multifocal Neuropathy: Expanding the Scope of Double Crush Syndrome.

Double crush syndrome (DCS), as it is classically defined, is a clinical condition composed of neurological dysfunction due to compressive pathology at multiple sites along a single peripheral nerve. The traditional definition of DCS is narrow in scope because many systemic pathologic processes, such as diabetes mellitus, drug-induced neuropathy, vascular disease and autoimmune neuronal damage, can have deleterious effects on nerve function. Multifocal neuropathy is a more appropriate term describing the multiple etiologies (including compressive lesions) that may synergistically contribute to nerve dysfunction and clinical symptoms. This paper examines the history of DCS and multifocal neuropathy, including the epidemiology and pathophysiology in addition to principles of evaluation and management.

Aerobic and Cognitive Exercise (ACE) Pilot Study for Older Adults: Executive Function Improves with Cognitive Challenge While Exergaming.

Dementia cases are increasing worldwide; thus, investigators seek to identify interventions that might prevent or ameliorate cognitive decline in later life. Extensive research confirms the benefits of physical exercise for brain health, yet only a fraction of older adults exercise regularly. Interactive mental and physical exercise, as in aerobic exergaming, not only motivates, but has also been found to yield cognitive benefit above and beyond traditional exercise. This pilot study sought to investigate whether greater cognitive challenge while exergaming would yield differential outcomes in executive function and generalize to everyday functioning. Sixty-four community based older adults (mean age=82) were randomly assigned to pedal a stationary bike, while interactively engaging on-screen with: (1) a low cognitive demand task (bike tour), or (2) a high cognitive demand task (video game). Executive function (indices from Trails, Stroop and Digit Span) was assessed before and after a single-bout and 3-month exercise intervention. Significant group × time interactions were found after a single-bout (Color Trails) and after 3 months of exergaming (Stroop; among 20 adherents). Those in the high cognitive demand group performed better than those in the low cognitive dose condition. Everyday function improved across both exercise conditions. Pilot data indicate that for older adults, cognitive benefit while exergaming increased concomitantly with higher doses of interactive mental challenge.

Use of Gammaglobulin to Lower Elevated Natural Killer Cells in Patients with Recurrent Miscarriage.

OBJECTIVE: To evaluate the effectiveness of intravenous immunoglobulin (IVIG) in patients presenting with recurrent miscarriage and abnormally elevated natural killer (NK) cells. STUDY DESIGN: This retrospective patient controlled evidence level II-2 pilot study was conducted at Cohen Center, P.A., Medical City Dallas Hospital. Ninety women with a history of recurrent miscarriage (average, 5) and elevated NK cells were retrospectively evaluated to document the outcome of their treatment with IVIG. RESULTS: Of 90 women with elevated NK cells who received IVIG treatment, 78 (86.7%) became pregnant. Sixty-four (82.0%) of those pregnancies had a successful viable outcome. Fourteen (18.0%) gestations ended as first trimester miscarriages. CONCLUSION: We conclude at evidence level II-2 that, with adequate precautions, low-dose IVIG therapy is safe and effective for women with immunologic abortion and documented abnormally elevated NK cells.

Efficacy and safety of collagenase clostridium histolyticum in the treatment of proximal interphalangeal joints in dupuytren contracture: combined analysis of 4 phase 3 clinical trials.

PURPOSE: To examine the results of proximal interphalangeal (PIP) joint contractures from 4 phase 3 clinical trials of collagenase clostridium histolyticum (CCH) injection for Dupuytren contracture. METHODS: Patients enrolled in Collagenase Option for Reduction of Dupuytren I/II and JOINT I/II with one or more PIP joint contractures (20° to 80°) received CCH 0.58 mg/0.20 mL or placebo (Collagenase Option for Reduction of Dupuytren I/II only) injected directly into a palpable cord. The percentage of PIP joints achieving clinical success (0° to 5° of full extension), clinical improvement (50% or more reduction in baseline contracture), and range of motion improvement at 30 days after the first and last CCH injections was assessed. The PIP joint contractures were classified into low (40° or less) and high (more than 40°) baseline severity. Adverse events were recorded. RESULTS: A total of 506 adults (mean age, 63 ± 10 y; 80% male) received 1,165 CCH injections in 644 PIP joint cords (mean, 1.6 injections/cord). Most patients (60%) received 1 injection, with 24%, 16%, and 1% receiving 2, 3, and 4 injections, respectively. Clinical success and clinical improvement occurred in 27% and 49% of PIP joints after one injection and in 34% and 58% after the last injection. Patients with lower baseline severity showed greater improvement and response was comparable between fingers, as were improvements in range of motion. Adverse events occurring in more than 10% of patients were peripheral edema (58%), contusion (38%), injection site hemorrhage (23%), injection site pain (21%), injection site swelling (16%), and tenderness (13%). This incidence was consistent with data reported in phase 3 trials. Two tendon ruptures occurred. No further ruptures occurred after a modified injection technique was adopted. CONCLUSIONS: Collagenase clostridium histolyticum was effective and well tolerated in the short term in patients with Dupuytren PIP joint contractures. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

The Efficacy and Safety of Concurrent Collagenase Clostridium Histolyticum Injections for 2 Dupuytren Contractures in the Same Hand: A Prospective, Multicenter Study.

PURPOSE: To evaluate efficacy and safety of concurrent administration of 2 collagenase clostridium histolyticum (CCH) injections to treat 2 joints in the same hand with Dupuytren fixed flexion contractures (FFCs). METHODS: Patients with 2 or more contractures in the same hand caused by palpable cords participated in a 60-day, multicenter, open-label, phase 3b study. Two 0.58 mg CCH doses were injected into 1 or 2 cords in the same hand (1 injection per affected joint) during the same visit. Finger extension was performed approximately 24, 48, or 72 or more hours later. Changes in FFC and range of motion, incidence of clinical success (FFC ≤ 5°), and adverse events (AEs) were summarized. RESULTS: The study enrolled 715 patients (725 treated joint pairs), and 714 patients (724 joint pairs) were analyzed for efficacy. At day 31, mean total FFC (sum of 2 treated joints) decreased 74%, from 98° to 27°. Mean total range of motion increased from 90° to 156°. The incidence of clinical success was 65% in metacarpophalangeal joints and 29% in proximal interphalangeal joints. Most treatment-related AEs were mild to moderate, resolving without intervention; the most common were swelling of treated extremity, contusion, and pain in extremity. The incidence of skin lacerations was 22% (160 of 715). Efficacy and safety were similar regardless of time to finger extension. CONCLUSIONS: Collagenase clostridium histolyticum can be used to effectively treat 2 affected joints concurrently without a greater risk of AEs than treatment of a single joint, with the exception of skin laceration. The incidence of clinical success in this study after 1 injection per joint was comparable to phase 3 study results after 3 or more injections per joint. Two concurrent CCH injections may allow more rapid overall treatment of multiple affected joints, and the ability to vary the time between CCH injection and finger extension may allow physicians and patients greater flexibility with scheduling treatment.

Electronic, redox, and photophysical consequences of metal-for-carbon substitution in oligo-phenylene-ethynylenes.

The electronic structures, redox chemistry, and excited-state properties of tungsten-containing oligo-phenylene-ethynylenes (OPEs) of the form W[C(p-C6H4CC)n-1Ph](dppe)2Cl (n = 1-5; dppe =1,2-bis(diphenylphosphino)ethane) are reported and compared with those of organic analogues in order to elucidate the effects of metal-for-carbon substitution on OPE bonding and electronic properties. Key similarities between the metallo- and organic OPEs that bear on materials-related functions include their nearly identical effective conjugation lengths, reduction potentials, and π* orbital energies and delocalization. In addition to these conserved properties, the tungsten centers endow OPEs with reversible one-electron oxidation chemistry and long-lived emissive triplet excited states that are not accessible to organic OPEs. The electronic similarities and differences between metallo- and organic OPEs can be understood largely on the basis of π/π* orbital energy matching between tungsten and organic PE fragments and the introduction of an orthogonal mid-π/π*-gap d orbital in metallo-OPEs. These orbital energies can be tuned by varying the supporting ligands; this provides a means to rationally implement and control the emergent properties of metallo-OPE materials.

Efficacy and safety of concurrent collagenase clostridium histolyticum injections for multiple Dupuytren contractures.

PURPOSE: To assess the safety and efficacy of 2 concurrent injections of collagenase clostridium histolyticum (CCH) in the same hand to treat multiple Dupuytren flexion contractures. METHODS: In a multicenter, open-label phase IIIb study, 60 patients received two 0.58-mg CCH doses injected into cords affecting 2 joints in the same hand during 1 visit, followed by finger extension approximately 24 hours later. Efficacy at postinjection day 30 (change in flexion contracture and active range of motion, patient satisfaction, physician-rated improvement, and rates of clinical success [flexion contracture 5° or less]) and adverse events were summarized. RESULTS: The concurrent injections were most commonly administered in cords affecting metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints on the same finger (47%) or 2 MCP joints on different fingers of the same hand (37%). Mean total (sum of the 2 treated joints) flexion contracture decreased 76%, from 87° to 24° (MCP joints: 86%; PIP joints: 66%). Mean total range of motion increased from 100° to 161°. Clinical success was 76% for MCP joints and 33% for PIP joints. Most patients were very satisfied (60%) or quite satisfied (28%) with treatment. Most investigators rated treated joints as very much improved (55%) or much improved (37%). The most common treatment-related adverse events (> 75% of patients) were contusion, pain in extremity, and edema peripheral (local edema). Most adverse events were mild to moderate in severity. Serious complications included 1 pulley rupture related to study medication and 1 flexor tendon rupture (following conclusion of the study). There were no systemic complications. CONCLUSIONS: Results suggest that 2 affected joints can be effectively and safely treated with concurrent CCH injections. There was an increased incidence of some adverse events with concurrent treatment (pruritus, lymphadenopathy, blood blister, and skin laceration) compared with treatment of a single joint. High degrees of patient satisfaction and physician-rated improvement were reported. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Dupuytren contracture recurrence following treatment with collagenase clostridium histolyticum (CORDLESS study): 3-year data.

PURPOSE: To evaluate long-term efficacy and safety of collagenase clostridium histolyticum (CCH) after the third year of a 5-year nontreatment follow-up study, Collagenase Option for Reduction of Dupuytren Long-Term Evaluation of Safety Study. METHODS: This study enrolled Dupuytren contracture patients from 5 previous clinical studies. Beginning 2 years after their first CCH injection, we re-evaluated patients annually for joint contracture and safety. Recurrence in a previously successfully treated joint (success = 0° to 5° contracture after CCH administration) was defined as 20° or greater worsening in contracture in the presence of a palpable cord or medical/surgical intervention to correct new or worsening contracture. We assessed partially corrected joints (joints reduced 20° or more from baseline contracture but not to 0° to 5°) for nondurable response, also defined as 20° or greater worsening of contracture or medical/surgical intervention. RESULTS: Of 1,080 CCH-treated joints (648 metacarpophalangeal [MCP]; 432 proximal interphalangeal [PIP]; n = 643 patients), 623 (451 MCP, 172 PIP) had achieved 0° to 5° contracture in the original study. Of these joints, 35% (217 of 623) recurred (MCP 27%; PIP 56%). Of these recurrences, an intervention was performed in 7%. Of the 1,080 CCH-treated joints, 301 were partially corrected in the original study. Of these, 50% (150 of 301; MCP: 38% [57 of 152]; PIP: 62% [93 of 149]) had nondurable response. We identified no new long-term or serious adverse events attributed to CCH during follow-up. Anti-clostridial type I collagenase and/or anti-clostridial type II collagenase antibodies were reported for 96% or more of patients who received 2 or more CCH injections and 82% who received 1 injection. CONCLUSIONS: The recurrence rate, which is comparable to other standard treatments, and the absence of long-term adverse events 3 years after initial treatment indicate that CCH is an effective and safe treatment for Dupuytren contracture. Most successfully treated joints had a contracture well below the threshold for surgical intervention 3 years after treatment. Recurrence rates among successfully treated joints were lower than nondurable response rates among partially corrected joints. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

An accessory limb with lipomyelomeningocele in a male.

At 7 months, an infant born with a third limb attached to a lumbosacral mass with an associated lipomyelomeningocele underwent removal of the limb and spinal cord detethering. Depending on the complexity of the pathology and proximity of the limb to viscera, consultation with neurosurgical and surgical colleagues is recommended.

Brain Health Indicators Following Acute Neuro-Exergaming: Biomarker and Cognition in Mild Cognitive Impairment (MCI) after Pedal-n-Play (iPACES).

Facing an unrelenting rise in dementia cases worldwide, researchers are exploring non-pharmacological ways to ameliorate cognitive decline in later life. Twenty older adults completed assessments before and after a single bout of interactive physical and cognitive exercise, by playing a neuro-exergame that required pedaling and steering to control progress in a tablet-based video game tailored to impact executive function (the interactive Physical and Cognitive Exercise System; iPACES v2). This study explored the cognitive and biomarker outcomes for participants with mild cognitive impairment (MCI) and normative older adults after 20 min of pedal-to-play exercise. Neuropsychological and salivary assessments were performed pre- and post-exercise to assess the impact. Repeated-measures ANOVAs revealed significant interaction effects, with MCI participants experiencing greater changes in executive function and alpha-amylase levels than normative older adults; within-group changes were also significant. This study provides further data regarding cognitive effects and potential mechanisms of action for exercise as an intervention for MCI.

Ground-state and excited-state structures of tungsten-benzylidyne complexes.

The molecular structure of the tungsten-benzylidyne complex trans-W(≡CPh)(dppe)(2)Cl (1; dppe = 1,2-bis(diphenylphosphino)ethane) in the singlet (d(xy))(2) ground state and luminescent triplet (d(xy))(1)(π*(WCPh))(1) excited state (1*) has been studied using X-ray transient absorption spectroscopy, X-ray crystallography, and density functional theory (DFT) calculations. Molecular-orbital considerations suggest that the W-C and W-P bond lengths should increase in the excited state because of the reduction of the formal W-C bond order and decrease in W→P π-backbonding, respectively, between 1 and 1*. This latter conclusion is supported by comparisons among the W-P bond lengths obtained from the X-ray crystal structures of 1, (d(xy))(1)-configured 1(+), and (d(xy))(2) [W(CPh)(dppe)(2)(NCMe)](+) (2(+)). X-ray transient absorption spectroscopic measurements of the excited-state structure of 1* reveal that the W-C bond length is the same (within experimental error) as that determined by X-ray crystallography for the ground state 1, while the average W-P/W-Cl distance increases by 0.04 Å in the excited state. The small excited-state elongation of the W-C bond relative to the M-E distortions found for M(≡E)L(n) (E = O, N) compounds with analogous (d(xy))(1)(π*(ME))(1) excited states is due to the π conjugation within the WCPh unit, which lessens the local W-C π-antibonding character of the π*(WCPh) lowest unoccupied molecular orbital (LUMO). These conclusions are supported by DFT calculations on 1 and 1*. The similar core bond distances of 1, 1(+), and 1* indicates that the inner-sphere reorganization energy associated with ground- and excited-state electron-transfer reactions is small.

Multiple concurrent collagenase clostridium histolyticum injections to Dupuytren's cords: an exploratory study.

BACKGROUND: Dupuytren's contracture (DC) is a progressive fibroproliferative disorder characterized by development of nodules and collagen cords within the palmar fascia of the hand. Collagenase clostridium histolyticum (CCH) is currently approved in adults with DC for the nonsurgical treatment of a single palpable cord during a 30-day treatment cycle. This open-label pilot study was designed to examine the safety, efficacy, and multiple-dose pharmacokinetics of injecting two cords (affected joints) with multiple doses of CCH concurrently into the same hand in subjects with DC and multiple contractures. METHODS: Twelve subjects with DC were enrolled, each with ≥3 contractures caused by palpable cords. Efficacy assessments were taken 30 days after treatment and adverse events (AEs) were recorded throughout. In the first treatment period, all subjects were injected with a single dose of CCH (0.58 mg) into a single cord. The same subjects entered a second treatment period 30 days later, where two different cords (affected joints) were injected concurrently on the same hand. A finger extension procedure was performed 24 hours after each administration of CCH to disrupt the enzymatically weakened cord. RESULTS: For metacarpophalangeal (MP) joints, mean contracture reduction per joint treated was 29.0 ± 20.7 degrees following single injection vs 30.3 ± 10.9 degrees per treated joint following multiple injections. For proximal interphalangeal (PIP) joints, mean reduction in contracture was 30.7 ± 21.1 and 22.1 ± 4.9 degrees per treated joint, respectively, for the two periods. All patients (100%) were either "quite satisfied" or "very satisfied" following either treatment cycle. The most common treatment-related AEs were edema peripheral, contusion, and pain in the treated extremity; the differences in severity for local effects of the injections were minimal between treatment periods. No serious treatment-related AEs or systemic complications were reported. CONCLUSION: These results provide preliminary evidence that two cords (affected joints) can be treated concurrently with CCH with similar efficacy and safety as cords treated individually in a sequential fashion. Multiple concurrent injections would eliminate the 30-day wait between single treatments and allow for rapid and effective treatment of patients with multiple affected joints, a significant advantage for both patient and physician. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry #ACTRN12610001045000.