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Introduction: Talquetamab, a bispecific antibody targeting GPRC5D × CD3, is approved for the treatment of patients with triple-class -exposed (TCE) relapsed/refractory multiple myeloma (RRMM) on the basis of the results from the phase I/II MonumenTAL-1 trial. The relative effectiveness of talquetamab vs. real-world physician's choice of therapy (RWPC) was assessed using adjusted comparisons., Methods: An external control arm for MonumenTAL-1 (subcutaneously administered talquetamab 0.4 mg/kg weekly [QW] and 0.8 mg/kg every other week [Q2W]) was created from two observational real-world studies: LocoMMotion and MoMMent. Imbalances in baseline covariates were adjusted using inverse probability weighting. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), ≥ very good partial response (VGPR), and ≥ complete response (CR); odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional hazards model., Results: After reweighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, patients treated with talquetamab QW (n = 143) had significantly improved outcomes vs. RWPC; RRs were ORR 2.67, p < 0.0001; ≥ VGPR 4.70, p < 0.0001; ≥ CR 78.05, p = 0.0002; and HRs were PFS 0.52, p < 0.0001; TTNT 0.48, p < 0.0001; OS 0.36, p < 0.0001. Patients treated with talquetamab Q2W (n = 145) also had significantly improved outcomes vs. RWPC; RRs were ORR 2.62, p < 0.0001; ≥ VGPR 5.04, p < 0.0001; ≥ CR 101.14, p = 0.0002; and HRs were PFS 0.40, p < 0.0001; TTNT 0.39, p < 0.0001; OS 0.37, p < 0.0001., Conclusion: Effectiveness of talquetamab for both schedules was significantly better than RWPC for ORR, ≥ VGPR, ≥ CR, PFS, OS, and TTNT, highlighting its clinical benefit for patients with TCE RRMM., Trial Registration: MonumenTAL-1, ClinicalTrials.gov identifier NCT03399799/NCT04634552; LocoMMotion, ClinicalTrials.gov identifier NCT04035226; MoMMent, ClinicalTrials.gov identifier NCT05160584., (© 2024. The Author(s).)

Objectives: Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing progressive organ dysfunction and death. Recent studies suggest that hematologic response may be an important prognostic indicator of overall survival (OS) in AL amyloidosis. The aim of this study was to evaluate the trial-level association between hematologic complete response (CR) or very good partial response or better (≥ VGPR) and OS in newly diagnosed patients., Methods: Studies were identified via systematic literature review. Pooled effect estimates were generated by a random-effects model., Results: Nine observational studies reporting hematologic CR or ≥VGPR and OS hazard ratios (HRs) were included in the meta-analysis. Achieving hematologic CR was associated with improved OS (HR, 0.21; 95% confidence interval [CI] 0.13-0.34). Achieving ≥ VGPR was also associated with improved OS (HR 0.21; 95% CI 0.17-0.26). Results of a sensitivity analysis excluding one outlier study revealed no heterogeneity and a better overall HR estimate. Potential limitations of this meta-analysis include the small number of eligible studies (consistent with the rarity of the disease) and inconsistencies in reporting of results., Conclusions: Overall, our findings support the use of deep hematologic response (CR or ≥VGPR) as a clinical trial endpoint in newly diagnosed AL amyloidosis. This study provides evidence that early hematologic response is a strong patient-level surrogate for long-term OS in patients with AL amyloidosis receiving frontline therapy. Structured data collection of depth of response in future trials will further strengthen these observations.

Introduction: Most classification systems for lateral discoid meniscus do not evaluate instability of the meniscal peripheral rim. Considerable variability in the prevalence of peripheral rim instability has been published, and it appears that instability is underestimated. The purpose of this study was: first, to evaluate the prevalence of peripheral rim instability and its location in the symptomatic lateral discoid meniscus, and second, to investigate if patient age or type of discoid meniscus are possible risk factors for instability., Methods: A cohort of 78 knees that underwent operative treatment due to symptomatic discoid lateral meniscus was analyzed retrospectively for the rate and location of peripheral rim instability., Results: Out of the 78 knees, 57.7% (45) had a complete and 42.3% (33) had an incomplete lateral meniscus. The prevalence of peripheral rim instability in symptomatic lateral discoid menisci was 51.3%, and with 32.5%, the anterior attachment was most commonly affected, followed by the posterior (30%) and central (10%) attachment. 27.5% of the tested menisci were unstable anteriorly and posteriorly. There was no significant difference in the prevalence of rim instability between the type of discoid menisci (complete vs. incomplete), nor was there a significant correlation for age as a risk factor for instability., Conclusion: The discoid lateral meniscus has a high prevalence and variable location of peripheral rim instability. Meniscal rim stability must be tested and addressed cautiously in all parts and in all types of discoid lateral menisci during operative treatment., (© 2023. The Author(s).)

Introduction: Acromioclavicular joint dislocations (ACD) are one of the most common shoulder injuries. There is no consensus in how to treat higher graded ACD ≥ Rockwood grade III. This study compares operative versus conservative treatment regarding costs and clinical outcome parameters., Materials and Methods: This retrospective, consecutive case-control-study includes 14 patients. Seven operatively treated patients were matched, by Rockwood grade, with seven conservatively treated patients. The cost was extracted out of the clinical- and insurance-based cost sheets and furthermore these include the loss of earnings. Clinical examination, demographic data as well as different outcome-questionnaires were recorded., Results: There were no significant differences between operative and conservative treated patients for outcome Questionnaires. Of note, there was a significantly higher incidence of tenderness over the AC-joint (p = 0.0038) postoperatively. As expected, economical evaluation showed various findings in favor of the conservative treatment. The costs for medical services (11012.39vs.1163.81USD; p = 0.0061), days of hospitalization (3.3vs.0days; p < 0.0001); total cost for medical treatment (30262.17 vs. 7833.82 USD; p = 0.0358) were significantly higher in the operative group., Conclusion: Even with a limited case number and a retrospective study design almost all clinical results were equal in both groups. Operative therapy of higher graded ACDs (Rockwood > III) compared to conservative is economically inefficient. Under consideration of clinical comparable results, indications for operative treatment should be set very carefully., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Impaired hip kinematics and kinetics may incite patellar instability. This study tested the hypothesis that hip adduction and internal rotation angles during gait are higher in adolescents with recurrent patellar dislocations compared to healthy controls., Material and Methods: Case-control study. Eighty-eight knees (67 patients) with recurrent patellar dislocation (mean age 14.8 years ± 2.8 SD) were compared to 54 healthy knees (27 individuals, 14.9 years ± 2.4 SD). Peak hip, knee and pelvis kinematics and kinetics were captured using 3D-gait analysis (VICON, 12 cameras, 200 Hz, Plug-in-Gait, two force plates) and compared between the two groups. One cycle (100%) consisted of 51 data points. The mean of six trials was computed., Results: Peak hip adduction angles and abduction moments were significantly higher in patients with recurrent patellar dislocation compared to the control group (p < 0.001 and 0.002, respectively). Peak internal hip rotation did not differ significantly., Conclusion: Elevated hip adduction angles and higher hip abduction moments in gait of adolescents with recurrent patellar dislocation may indicate an impaired function of hip abductors that contributes to patellar instability., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: We compared the effectiveness of teclistamab versus real-world physician's choice of therapy (RWPC) in triple-class exposed relapsed/refractory multiple myeloma. Materials & methods: MajesTEC-1 eligibility criteria were applied to the RWPC cohort. Baseline covariate imbalances were adjusted using inverse probability of treatment weighting. Overall survival, progression-free survival and time to next treatment were compared. Results: After inverse probability of treatment weighting, baseline characteristics were similar between cohorts (teclistamab, n = 165; RWPC, n = 364 [766 observations]). Teclistamab treated patients had numerically better overall survival (hazard ratio [HR]: 0.82 [95% CI: 0.59-1.14]; p = 0.233) and significantly greater progression-free survival (HR: 0.43 [0.33-0.56]; p < 0.0001) and time to next treatment (HR: 0.36 [0.27-0.49]; p < 0.0001) versus the RWPC cohort. Conclusion: Teclistamab offered clinical benefit over RWPC in triple-class exposed relapsed/refractory multiple myeloma.

Background: This study characterised real-world treatment patterns, clinical outcomes, and cost-of-illness in patients with light-chain (AL) amyloidosis., Methods: Data were extracted from the US-based Optum® EHR and Clinformatics® Data Mart (claims) databases (2008-2019) for patients newly diagnosed with AL amyloidosis and who initiated anti-plasma cell therapies. Healthcare resource utilisation (HCRU) and related costs were compared across lines of therapy (LOT). Incidences of cardiac and renal failure were evaluated using the Kaplan-Meier method., Results: About 1347 patients (EHR, n  = 776; claims, n  = 571) were included. Median age was 68 years; 56.8% were male. At initial diagnosis, 33.1% and 15.1% of patients had cardiac and renal failure, respectively. Most patients received bortezomib-containing treatment in LOT1 (69%); bortezomib-cyclophosphamide-dexamethasone was most common (26%). HCRU was similar across LOTs. Mean per-patient-per-month and per-patient-per-LOT costs were $19,343 and $105,944 for LOT1, $19,183 and $95,793 for LOT2, and $16,611 and $128,446 for LOT3, respectively. Costs were primarily driven by anti-plasma cell therapies, outpatient visits, and hospitalisations. The 5-year cardiac and renal failure rates following initial diagnosis were 64.5% and 39.0%, respectively., Conclusion: AL amyloidosis is associated with substantial costs and suboptimal outcomes, highlighting the need for new therapeutic approaches to prevent organ deterioration, and reduce disease burden.

Background: Because patients with newly diagnosed multiple myeloma (NDMM) do not always receive any treatment beyond first-line (1L) therapy, it is imperative that patients receive the best treatment in the 1L setting. However, the optimal initial treatment remains to be identified. We performed a clinical simulation to assess potential outcomes with different treatment sequences., Patients and Methods: We used a partitioned survival model to compare overall survival (OS) with (1) daratumumab, lenalidomide, and dexamethasone (D-Rd) in 1L followed by a pomalidomide- or carfilzomib-based regimen in second line (2L) versus (2) bortezomib, lenalidomide, and dexamethasone (VRd) in 1L followed by a daratumumab-based regimen in 2L versus (3) lenalidomide and dexamethasone (Rd) in 1L followed by a daratumumab-based regimen in 2L. Probabilities of transition between health states (1L, 2L+, and death) were based on published clinical data and real-world data from the Flatiron Health database. The proportion of patients discontinuing treatment after 1L (attrition rates) in the base case was estimated with a binomial logistic model using data from the MAIA trial., Results: Using D-Rd in 1L conferred a longer median OS compared with delaying daratumumab-based regimens until 2L after VRd or Rd, respectively (8.9 [95% CrI 7.58-10.42] vs. 6.92 [5.92-8.33] or 5.75 [4.50-7.25] years). Results of scenario analyses were consistent with the base case., Conclusion: Our simulation, which incorporates clinically representative treatments and attrition rates, supports the use of D-Rd as initial therapy, rather than delaying the use of daratumumab until later lines of therapy, in patients with transplant-ineligible NDMM., (© The Author(s) 2023. Published by Oxford University Press.)

Background: The efficacy and safety of teclistamab in patients with RRMM who received ≥3 prior lines of therapy and were triple-class exposed (TCE) are being evaluated in the single-arm, multicohort, phase I/II MajesTEC-1 trial (NCT04557098). We evaluated the comparative effectiveness of teclistamab versus physician's choice (PC) of therapy in TCE RRMM patients., Methods: Individual patient-level data from MajesTEC-1 patients who received teclistamab (1.5 mg/kg weekly; clinical cutoff March 16, 2022) were included. An external control arm was created from patients in long-term follow-up of 4 clinical trials of daratumumab who were treated with PC therapy after discontinuation of trial treatments. In the primary analysis, inverse probability of treatment weighting was used to adjust for imbalances in 9 baseline covariates. A fully adjusted model included 5 additional prognostic factors. Outcomes included overall response rate (ORR), very good partial response or better (≥VGPR) rate, overall survival (OS), progression-free survival (PFS), and time to next treatment (TTNT)., Results: After adjustment, baseline characteristics were balanced between cohorts. In the primary analysis, outcomes were significantly improved with teclistamab versus PC: ORR (OR [95% CI] 4.81 [3.04-7.72]; P < .0001); ≥VGPR rate (OR, 12.07 [6.91-22.11]; P < .0001); OS (HR, 0.54 [0.40-0.73]; P < .0001); PFS (HR, 0.59 [0.46-0.78]; P = .0001); and TTNT (HR, 0.32 [0.24-0.42]; P < .0001). Results of the fully adjusted model were consistent with the primary analysis., Conclusion: Teclistamab showed significantly improved effectiveness versus PC on all outcomes, highlighting its clinical benefit in patients with TCE RRMM and limited treatment options., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In nursing homes, food is part of the care provided to residents, causing it to be strictly organised within the institutional framework. Moreover, once food has been integrated into the institutional logic, structural and economic aspects regarding organisation of food and eating may dictate individual and social needs, as a theoretical perspective informed by Goffman's notion of the 'total social institution' suggests. This paper describes nursing home residents' practices of dealing with meal requirements in two Austrian nursing homes, to understand how food integrates into the daily routine and how the institutional setting influences the social and material arrangement of food., Methods: An ethnographic design was chosen to gain an in-depth understanding. Two urban nursing homes were studied over 21 months (approx. 800 h of participant observation and ethnographic interviews collected). Data analysis took place iteratively, following Grounded Theory strategies., Results: As the thick descriptions resulting from this procedure show, observing everyday practices of eating in nursing homes reveals complex dimensions of residents being subject to institutional logics, and also demonstrates that residents develop elaborate strategies to deal with the institutional circumstances., Conclusion: A better understanding of the resulting tensions between the restrictions of living in a formal organisation and the agencies of residents described, may contribute to better understanding the effects of structural constraints and to designing more flexible processes., (© 2022. The Author(s).)

Background: Shortcomings to tibial-side fixation have been reported as causes of failure after anterior cruciate ligament reconstruction. Adjustable-loop suspensory devices have become popular; however, no comparison with hybrid fixation (ie, interference screw and cortical button) exists to our knowledge., Purpose: The purpose of this study was to compare the biomechanical properties of adjustable loop devices (ALDs) in full-tunnel and closed-socket configurations in relation to hybrid fixation. We hypothesized that primary stability of fixation by a tibial ALD will not be inferior to hybrid fixation., Study Design: Controlled laboratory study., Methods: Tibial fixation of a quadrupled tendon graft was biomechanically investigated in a porcine tibia-bovine tendon model using 5 techniques (n = 6 specimens each). The tested constructs included hybrid fixation with a cortical fixation button and interference screw (group 1), single cortical fixation with the full-tunnel technique using an open-suture strand button (group 2) or an ALD (group 3), or closed-socket fixation using 2 different types of ALDs (groups 4 and 5). Each specimen was evaluated using a materials testing machine (1000 cycles from 50-250 N and pull to failure). Force at failure, cyclic displacement, stiffness, and ability to pretension the graft during insertion were compared among the groups., Results: No differences in ultimate load to failure were found between the ALD constructs (groups 3, 4, and 5) and hybrid fixation (group 1). Cyclic displacement was significantly higher in group 2 vs all other groups ( P < .001); however, no difference was observed in groups 3, 4, and 5 as compared with group 1. The remaining tension on the construct after fixation was significantly higher in groups 3 and 4 vs groups 1, 2, and 5 ( P < .02 for all comparisons), irrespective of whether a full-tunnel or closed-socket approach was used., Conclusion: Tibial anterior cruciate ligament graft fixation with knotless ALDs achieved comparable results with hybrid fixation in the full-tunnel and closed-socket techniques. The retention of graft tension appears to be biomechanically more relevant than tunnel type., Clinical Relevance: The study findings emphasize the importance of the tension at which fixation is performed., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: E.B. is an employee of and holds stock in ZuriMED Technologies. J.S. holds stock in ZuriMed Technologies. S.F.F. has received consulting fees from Medacta. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Social support is associated prospectively with cognitive decline and dementia among the elderly; however, little is known about the impact of social support on healthy neurological aging. The current study investigates whether perceived social support has an influence on neurological health among a large sample of healthy postmenopausal women. Social support and neuropsychological outcomes were measured annually for six years through the Women's Health Initiative Study of Cognitive Aging. In postmenopausal women, higher perceived social support was associated with significantly better overall neuropsychological functioning at baseline, especially in the domains of short-delay figural memory, short-delay verbal memory, and semantic fluency. No significant associations were found between social support and longitudinal changes in neuropsychological function over a median follow-up period of six years. Additionally, there was no significant relationship between social support and regional brain volumes. These findings suggest that social support is related to performance in a subset of neuropsychological domains and contributes to the existing literature that points to the importance of social support as a modifiable lifestyle factor that has the potential to help protect against the decline of cognitive aging, specifically among older adult women.

Introduction: Many treatment regimens have been evaluated in transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). The objective of this study was to compare the efficacy of relevant therapies for the treatment of TIE patients with NDMM., Methods: Progression-free survival (PFS) and overall survival (OS) from large randomised controlled trials (RCTs) evaluating different treatment options for TIE patients with NDMM were compared in a network meta-analysis (NMA). The NMA includes recent primary and long-term OS readouts from SWOG S0777, ENDURANCE, MAIA, and ALCYONE. Relevant trials were identified through a systematic literature review. Relative efficacy measures (i.e., hazard ratios [HRs] for PFS and OS) were extracted and synthesised in random-effects NMAs., Results: A total of 122 publications describing 45 unique RCTs was identified. Continuous lenalidomide/dexamethasone (Rd) was selected as the referent comparator. Daratumumab-containing treatments (daratumumab/lenalidomide/dexamethasone [D-Rd], daratumumab/bortezomib/melphalan/prednisone [D-VMP]) and bortezomib/lenalidomide/dexamethasone (VRd) had the highest probabilities of being more effective than Rd continuous for PFS (HR: D-Rd, 0.53; D-VMP, 0.57, VRd, 0.77) and OS (HR: D-Rd, 0.68; VRd, 0.77, D-VMP, 0.78). D-Rd had the highest chance of being ranked as the most effective treatment with respect to PFS and OS. Results using a smaller network focusing on only those regimens that are relevant in Europe were consistent with the primary analysis., Conclusions: These comparative effectiveness data may help inform treatment selection in TIE patients with NDMM., (© 2022. The Author(s).)

Introduction: Treatment of amyloid light-chain (AL) amyloidosis, a rare disease with a <5-year lifespan, remains challenging. This systematic literature review (SLR) aimed to evaluate the current evidence base in AL amyloidosis. Methods: Literature searches on clinical, health-related quality of life, economic and resource use evidence were conducted using the Embase, MEDLINE and Cochrane databases as well as gray literature. Results: This SLR yielded 84 unique studies from: five randomized controlled trials; 54 observational studies; 12 health-related quality of life studies, none with utility values; no economic evaluation studies; and 16 resource use studies, none with indirect costs. Conclusion: This SLR highlights a paucity of published literature relating to randomized controlled trials, utility values, economic evaluations and indirect costs in AL amyloidosis.

Introduction: Despite high rectal cancer recurrence rates, knowledge on post-treatment surveillance utilization is limited. Hence, this study aims to estimate patterns of post-treatment surveillance and determine associated factors., Patients and Methods: Retrospective study of 1,024 SEER-Medicare patients >65 years old diagnosed with stage II/III rectal cancer between 2007-2013. Logistic regression was used to determine factors associated with ≥1 colonoscopy, ≥2 physician visits, ≥2 carcinoembryonic antigen (CEA) tests and ≥2 computed tomographic colonography (CT) within 14 months after primary treatment., Results: Fifty-five percent had ≥1 colonoscopy, 54% had ≥2 physician visits, 47% had ≥2 CEA tests and 20% had ≥2 CTs. In multivariable logistic models, younger age and receipt of chemoradiation therapy (vs none) were significant across all surveillance procedures while clinical factors such as comorbidity were not. Being married (OR=1.69; 95% CI: 1.26-2.26) and proximity to a high-volume hospital (≤15 vs >30 minutes, OR=1.56; 95% CI: 1.00-2.43) were associated with ≥1 colonoscopy. Female gender (OR=1.56; 95% CI: 1.17-2.09), being married (OR=1.56; 95% CI: 1.17-2.08), white race (OR=1.79; 95% CI: 1.23- 2.62) and surgery from high-volume surgeon (OR=1.47; 95% CI: 1.06-2.04) were associated with ≥2 physician visits. Female gender (OR=1.45; 95% CI: 1.08-1.95), being married (OR=1.46; 95% CI: 1.08-1.96) and surgery from high-volume surgeon (OR=1.55; 95% CI: 1.10-2.17) had higher ≥2 CEA tests., Conclusions: Post-treatment surveillance remains low but is more common among younger patients and recipients of chemoradiation. Distinct profiles of patient characteristics and provider volume were associated with individual surveillance procedures suggesting the need for multicomponent strategies to increase surveillance.

Purpose: To evaluate the association of in-hospital surgical bleeding events with the outcomes of hospital length of stay (LOS), days spent in critical care, complications, and mortality among patients undergoing neoplasm-directed surgeries in English hospitals., Patients and Methods: This is a retrospective cohort study using English hospital discharge data (Hospital Episode Statistics [HES]) linked to electronic health records (Clinical Practice Research Datalink [CPRD]). HES includes information on patient demographics, admission and discharge dates, diagnoses and procedures, days spent in critical care, and discharge status. CPRD includes information on patient demographics, diagnoses and symptoms, drug exposures, vaccination history, and laboratory tests. Patients aged ≥18 years who underwent selected neoplasm-directed surgeries between 1-Jan-2010 and 29-February-2016: hysterectomy, low anterior resection (LAR), lung resection, mastectomy, and prostate surgery were included. The primary independent variable was in-hospital surgical bleeding events identified by diagnosis of haemorrhage and haematoma complicating a procedure or reopening/re-exploration and surgical arrest of postoperative bleeding. Outcomes included LOS, days spent in critical care, in-hospital complications (diagnoses of infections, acute renal failure, vascular events), and in-hospital mortality, identified during surgery through discharge. Multivariable regression was used to examine the adjusted association of bleeding events with outcomes., Results: The study included 26,437 neoplasm-directed surgeries (hysterectomy=6092; LAR=2957; lung=1538; mastectomy=12,806; prostate=3044). Incidence proportions of bleeding events were: hysterectomy=1.9% (95% confidence interval=1.1-2.5%); LAR=3.0% (CI=2.3-3.6%); lung=1.8% (CI=1.1-2.5%); mastectomy=1.6% (CI=1.3-1.8%); prostate=1.0% (CI=0.6-1.3%). In adjusted analyses, bleeding events were associated with: prolonged LOS: 3.1 (CI=1.1-6.3) mastectomy to 5.7 (CI=3.6-8.2) LAR days longer; more days spent in critical care: 0.4 (CI=0.03-0.27) mastectomy to 6.5 (CI=2.5-13.6) hysterectomy days more; and higher incidence proportions of all examined complications; all P <0.05., Conclusion: This study quantifies a substantial clinical and healthcare resource utilization burden associated with surgical bleeding among patients undergoing neoplasm-directed surgery in England hospitals., Competing Interests: Stephen S. Johnston, Nadine Jamous, Sameer Mistry, Gaurav Gangoli, Walter Danker, and Eric Ammann are currently employed or were employed by Johnson & Johnson at the time this study was conducted. Gaurav Gangoli and Walter Danker were affiliated with Ethicon at the time the study was conducted. Eric Ammann was affiliated with Janssen at the time the study was conducted. Simran Jain was employed by Mu Sigma at the time the study was conducted. Simran Jain and Kingsley Hampton were consultants to Johnson & Johnson at the time that this research was conducted. The authors report no other conflicts of interest in this work., (© 2021 Johnston et al.)

Primary traumatic anterior shoulder dislocations can be associated with displaced anterior glenoid rim fractures. Nonoperative treatment of such fractures has been shown to have excellent results in a small cohort of patients; as such, we have been treating these fractures nonoperatively, regardless of fragment size and degree of displacement, provided that post-reduction computed tomography scans revealed an anteroposteriorly centered humeral head. The aim of this study was to analyze the medium- to long-term results of nonoperative treatment of displaced anterior glenoid rim fractures, assessing in particular the residual instability and development of osteoarthritis., Methods: In a 2-center study, 30 patients with a mean age of 48 years (range, 29 to 67 years) were evaluated clinically with use of the Subjective Shoulder Value, Constant score, American Shoulder and Elbow Surgeons score, and Western Ontario Shoulder Instability index, as well as radiographically with use of radiographs and computed tomography scans at a mean follow-up of 9 years (range, 5 to 14 years)., Results: Fracture-healing was documented in all patients. Seven patients (23%) had post-fracture onset of osteoarthritis (5 with Samilson grade I and 2 with Samilson grade IV). Of these, 1 patient had recurrent instability that was successfully treated with hemiarthroplasty 9 years after the index injury (relative Constant score, 101%), and was excluded from further analysis. No other patient had a recurrent redislocation, subluxation, or positive apprehension. The other 6 patients with new-onset radiographic osteoarthritis were pain-free (mean Constant score pain scale, 15 points) with good shoulder function (relative Constant score, 84% to 108%). A total of 26 patients (90%) rated their functional outcome as good or very good, and 3 patients (10%) rated it as fair. The mean relative Constant score was 97% (range, 61% to 108%), the mean American Shoulder and Elbow Surgeons score was 92 points (range, 56 to 100 points), and the mean Western Ontario Shoulder Instability index score was 126 points (range, 0 to 660 points). All patients returned to full-time work., Conclusions: Nonoperative treatment of anterior glenoid rim fractures following primary traumatic anterior shoulder dislocation results in excellent clinical outcomes with a very low rate of residual instability and, thus, treatment failure. Asymptomatic radiographic osteoarthritis occurred in roughly 1 of 4 patients., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A235)., (Copyright © 2020 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Purpose: To investigate if a trochleoplasty increases knee flexion angles and extensor moments in the gait of patients with patellar instability and to compare postoperative gait to a healthy control group., Methods: A bilateral dislocation group (6 patients) and a unilateral dislocation group (14 patients) were treated with bilateral and unilateral trochleoplasty, respectively. Kinematics and kinetics of the lower extremity were captured using 3D-gait analysis (VICON, 12 cameras, 200 Hz, plug-in-gait, two force plates). The mean of six trials was computed. The gait cycles were compared pre to postoperatively for each group. The gait of the two groups was compared to each other and the gait of a healthy population (54 knees)., Results: After trochleoplasty, the knee flexion angles and knee extensor moments only increased in the bilateral dislocation group, whereas the gait pattern of the unilateral dislocation group remained unchanged. Compared to the healthy population, the postoperative gait pattern of the bilateral dislocation group did not differ. In contrast, knee flexion angles and extensor moments of the unilateral dislocation group were still lower., Conclusion: In adolescents with bilateral recurrent patellar dislocations, trochleoplasty of both knees increases knee flexion angles and knee extensor moments comparable to normal gait. Unilateral symptomatic patients undergoing a unilateral trochleoplasty did not achieve normal walking. These findings point out that patellar instability should be considered as a bilateral problem, even in patients with unilateral dislocations., Level of Evidence: III.

Purpose: To evaluate the kinematics/kinetics of the ankle, knee, hip in the sagittal plane in adolescents with recurrent patellar dislocation in comparison to a healthy control., Methods: Case-control study. Eighty-eight knees (67 patients) with recurrent patellar dislocation (mean age 14.8 years ± 2.8 SD) were compared to 54 healthy knees (27 individuals, 14.9 years  ± 2.4 SD). Kinematics/kinetics of ankle, knee, hip, and pelvis were captured using 3D-gait analysis (VICON, 12 cameras, 200 Hz, Plug-in-Gait, two force plates). One cycle (100%) consisted of 51 data-points. The mean of six trials was computed., Results: The loading-response increased by 0.02 s ± 0.01SE (10.8%) with dislocations (0.98% of total gait, P < 0.01). The mid-stance-phase decreased equally (P < 0.01). Dislocation decreased knee flexion during the entire gait cycle (P < 0.01), with the largest difference during mid-stance (9.0° ± 7.2 SD vs. 18.5° ± 6.7 SD). Dislocation increased plantar-flexion during loading response 4.1° ± 0.4 SE with (P < 0.01), afterward, the dorsal-extension decreased 3.2° ± 0.3 SE, (P < 0.01). Dislocation decreased hip flexion during all phases (P < 0.01). Maximal difference: 7.5° ± 0.5 SE during mid-stance. 80% of all patients developed this gait pattern. Internal moments of the ankle increased, of the knee and hip decreased during the first part of stance., Conclusion: Recurrent patellar dislocation decreases knee flexion during the loading-response and mid-stance phase. A decreased hip flexion and increased plantar-flexion, while adjusting internal moments, indicate a compensation mechanism., Level of Evidence: III.

Background: The purpose of this study was to investigate the benefit of surgical anchor and/or suture removal and prolonged antibiotic therapy in acute and chronic infections of rotator cuff repair (RCIs)., Methods: A single-center cohort and case-control study (Cox regression) was performed. Outcome variables were remission of infection and postinfection reoperations due to failed tendon healing for mechanical causes. All analyses were performed with an emphasis on anchor and suture retention or removal., Results: We identified 54 primary RCIs (44 men; median age 54 years) that were surgically revised (10 by open débridement and 44 by arthroscopy). Twenty-eight (52%) were not intact on revision surgery (débridement) - 10 were partially and 18 totally re-ruptured. The median number of surgical revisions was 1 (range, 1-3), and the median duration of postsurgical antibiotic therapy was 75 days. After a minimal follow-up of 2 years, 8 infections (8/54, 15%) recurred. Twenty patients needed a revision surgery; in all of those 20 patients, intraoperative samples were negative for infection. By multivariate analysis, anchor removal at the first revision influenced neither remission (hazard ratio [HR] 0.9, 95% confidence interval [CI] 0.4-2.0) nor the need for later revision surgery due to mechanical sequelae (HR 0.6, 95% CI 0.1-1.4). The corresponding HRs for suture removal were 0.9 (95% CI 0.4-1.7) and 0.4 (95% CI 0.1-1.2). Likewise, the numbers of revision surgery (HR 0.5, 95% CI 0.2-1.3) and antibiotics beyond 6 weeks failed to influence remission (HR 1.1, 95% CI 0.4-3.1)., Conclusions: In our RCI cohort, the removal of anchors or sutures, repeated revision surgery, or an antibiotic therapy beyond 6 weeks failed to improve remission or to reduce sequelae., (Copyright © 2019 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Objective: Osteoarthritis is highly prevalent and, on aggregate, is one of the largest contributors to US spending on hospital-based health care. This study sought to examine body mass index (BMI)-related variation in the association of osteoarthritis with healthcare utilization and expenditures., Methods: This is a retrospective study using administrative insurance claims linked to electronic health records. Study patients were aged ≥ 18 years with ≥1 BMI measurement recorded in 2014, with the first ( index ) BMI ≥ 25 kg m -2 . Study outcomes and covariates were measured during a 1-year evaluation period spanning 6 months before and after index. Multivariable regression analyses examined the association of BMI with osteoarthritis prevalence, and the combined associations of osteoarthritis and BMI with osteoarthritis-related medication utilization, all-cause hospitalization, and healthcare expenditures., Results: A total of 256 459 patients (median age = 56 y) met study eligibility criteria; 14.8% (38 050) had osteoarthritis. In multivariable analyses, the adjusted prevalence of osteoarthritis increased with increasing BMI (12.7% in patients who were overweight [25.0-29.9 kg m -2 ] to 21.9% in patients with class III obesity [BMI ≥ 40 kg m -2 ], P < .001). Among patients with osteoarthritis, increasing BMI (from overweight to class III obesity) was associated with increased (all P < .01): utilization rates for analgesic medications (41.5-53.5%); rates of all-cause hospitalization (26.3%-32.0%); and total healthcare expenditures ($18 204-$23 372)., Conclusion: The prevalence and economic burden of osteoarthritis grow with increasing BMI; primary prevention of weight-related osteoarthritis and secondary weight management may help to alleviate this burden., Competing Interests: Stephen Johnston is an employee and stockholder of Johnson & Johnson. Eric Ammann is an employee of Johnson & Johnson. Robin Scamuffa was an employee and stockholder of Ethicon, a Johnson & Johnson company, at the time of this research. Jonathan Samuels has no financial interests to disclose. Andrew Stokes has received research funding from Ethicon, a Johnson & Johnson company, for an unrelated study. Elliott Fegelman was an employee and stockholder of Ethicon, a Johnson & Johnson company, at the time of this research. Carine Hsiao was an employee and stockholder of Ethicon, a Johnson & Johnson company, at the time of this research., (© 2019 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Background: Bleeding is a significant complication in cardiac surgery and is associated with substantial morbidity and mortality. This study evaluated the impact of bleeding on length of stay (LOS) and critical care utilization in a nationwide sample of cardiac surgery patients treated at English hospitals., Methods: Retrospective, observational cohort study using linked English Hospital Episode Statistics (HES) and Clinical Practice Research Datalink (CPRD) records for a nationwide sample of patients aged ≥18 years who underwent coronary artery bypass graft (CABG), valve repair/replacement, or aortic operations from January 2010 through February 2016. The primary independent variables were in-hospital bleeding complications and reoperation for bleeding before discharge. Generalized linear models were used to quantify the adjusted mean incremental difference [MID] in post-procedure LOS and critical care days associated with bleeding complications, independent of measured baseline characteristics., Results: The study included 7774 cardiac surgery patients (3963 CABG; 2363 valve replacement/repair; 160 aortic procedures; 1288 multiple procedures, primarily CABG+valve). Mean LOS was 10.7d, including a mean of 4.2d in critical care. Incidences of in-hospital bleeding complications and reoperation for bleeding were 6.7 and 0.3%, respectively. Patients with bleeding had longer LOS (MID: 3.1d; p < 0.0001) and spent more days in critical care (MID: 2.4d; p < 0.0001). Reoperation for bleeding was associated with larger increases in LOS (MID = 4.0d; p = 0.002) and days in critical care (MID = 3.2d; p = 0.001)., Conclusions: Among English cardiac surgery patients, in-hospital bleeding complications were associated with substantial increases in healthcare utilization. Increased use of evidence-based strategies to prevent and manage bleeding may reduce the clinical and economic burden associated with bleeding complications in cardiac surgery.

The production of biopolyols (sustainable, renewable and biodegradable precursors), is exclusively focused on the conventional chemical synthesis pathways, and currently, no polyols are produced by enzymatic processes at an industrial scale, because they are not competitive when compared to petrochemically based polyols due to the overall cost for their production. This can be mainly attributed to the high costs of commercial enzymes used in this process and their use is limited by their lack of stability during the bioprocess. Immobilization of enzymes gives the opportunity to converge two important features of enzymes: to increase the protein stability and to reuse enzyme as a catalyst. By this study, we were aiming to explore alternatives to commercially available enzymes. We investigated an effective hydrolytic route from epoxidized oils to polyols by applying lipolytic enzymes from Yarrowia lipolytica and Candida cylindracea immobilized onto fumed silica nanoparticles (fsNP) and those immobilized by the formation of cross-linked enzyme aggregates (CLEAs). Oxirane ring hydrolysis of epoxidized rapeseed oil catalyzed by lipase-fsNP and CLEAs was investigated with respect to various parameters (temperature, pH, concentrations, time of sorption and cross-linking, etc.). The highest conversions for oxirane ring hydrolysis were estimated for CLEA-Lip-derivatives (45-56%)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To investigate the relationship between aspirin and subclinical cerebrovascular heath, we evaluated the effect of chronic aspirin use on white matter lesions (WML) volume among women., Methods: Chronic aspirin use was assessed in 1365 women who participated in the Women's Health Initiative Memory Study of Magnetic Resonance Imaging. Differences in WML volumes between aspirin users and nonusers were assessed with linear mixed models. A number of secondary analyses were performed, including lobe-specific analyses, subgroup analyses based on participants' overall risk of cerebrovascular disease, and a dose-response relationship analysis., Results: The mean age of the women at magnetic resonance imaging examination was 77.6 years. Sixty-one percent of participants were chronic aspirin users. After adjusting for demographic variables and comorbidities, chronic aspirin use was nonsignificantly associated with 4.8% (95% CI: -6.8%, 17.9%) larger WML volumes. These null findings were confirmed in secondary and sensitivity analyses, including an active comparator evaluation where aspirin users were compared to users of nonaspirin nonsteroidal anti-inflammatory drugs or acetaminophen., Conclusions: There was a nonsignificant difference in WML volumes between aspirin users and nonusers. Further, our results suggest that chronic aspirin use may not have a clinically significant effect on WML volumes in women., (Published by Elsevier Inc.)

Enzymes immobilization is a useful way to allow enzyme reuse and increase their stability. A high redox potential laccase from Trametes versicolor (TvL) and a low redox potential, but commercially available low-cost laccase from Myceliophthora thermophila (MtL), were successfully immobilized and co-immobilized onto fumed silica nanoparticles (fsNP). Enzyme loads of 1.78 ± 0.07, 0.69 ± 0.03, and 1.10 ± 0.01 U/mg fsNP were attained for the optimal doses of TvL, MtL, and co-immobilized laccases, respectively. In general, the laccase-fsNP conjugates showed a higher resistance against an acidic pH value (i.e., pH 3), and a higher storage stability than free enzymes. In addition, immobilized enzymes exhibited a superior long-term stability than free laccases when incubated in a secondary effluent from a municipal wastewater treatment plant (WWTP). For instance, the residual activity after 2 weeks for the co-immobilized laccases and the mixture of free laccases were 40.2 ± 2.5% and 16.8 ± 1.0%, respectively. The ability of the laccase-fsNP to remove a mixture of (14)C-bisphenol A (BPA) and (14)C-sodium diclofenac (DCF) from spiked secondary effluents was assessed in batch experiments. The catalytic efficiency was highly dependent on both the microbial source and state of the biocatalyst. The high redox potential TvL in free form attained a four-fold higher percentage of BPA transformation than the free MtL. Compared to free laccases, immobilized enzymes led to much slower rates of BPA transformation. For instance, after 24 h, the percentages of BPA transformation by 1000 U/L of a mixture of free laccases or co-immobilized enzymes were 67.8 ± 5.2 and 27.0 ± 3.9%, respectively. Nevertheless, the use of 8000 U/L of co-immobilized laccase led to a nearly complete removal of BPA, despite the unfavorable conditions for laccase catalysis (pH ~ 8.4). DCF transformation was not observed for any of the enzymatic systems, showing that this compound is highly recalcitrant toward laccase oxidation under realistic conditions.

Background: 'Kneipp Therapy' (KT) is a form of Complementary and Alternative Medicine (CAM) that includes a combination of hydrotherapy, herbal medicine, mind-body medicine, physical activities, and healthy eating. Since 2007, some nursing homes for older adults in Germany began to integrate CAM in the form of KT in care. The study investigated how KT is used in daily routine care and explored the health status of residents and caregivers involved in KT., Methods: We performed a cross-sectional pilot study with a mixed methods approach that collected both quantitative and qualitative data in four German nursing homes in 2011. Assessments in the quantitative component included the Quality of Life in Dementia (QUALIDEM), the Short Form 12 Health Survey (SF-12), the Barthel-Index for residents and the Work Ability Index (WAI) and SF-12 for caregivers. The qualitative component addressed the residents' and caregivers' subjectively experienced changes after integration of KT. It was conceptualized as an ethnographic rapid appraisal by conducting participant observation and semi-structured interviews in two of the four nursing homes., Results: The quantitative component included 64 residents (53 female, 83.2 ± 8.1 years (mean and SD)) and 29 caregivers (all female, 42.0 ± 11.7 years). Residents were multimorbid (8 ± 3 diagnoses), and activities of daily living were restricted (Barthel-Index 60.6 ± 24.4). The caregivers' results indicated good work ability (WAI 37.4 ± 5.1), health related quality of life was superior to the German sample (SF-12 physical CSS 49.2 ± 8.0; mental CSS 54.1 ± 6.6). Among both caregivers and residents, 89% considered KT to be positive for well-being.The qualitative analysis showed that caregivers perceived emotional and functional benefits from more content and calmer residents, a larger variety in basic care practices, and a more self-determined scope of action. Residents reported gains in attention and caring, and recognition of their lay knowledge., Conclusion: Residents showed typical characteristics of nursing home inhabitants. Caregivers demonstrated good work ability. Both reported to have benefits from KT. The results provide a good basis for future projects, e.g. controlled studies to evaluate the effects of CAM in nursing homes.

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been found to be epidemiologically and microbiologically distinct from healthcare-associated MRSA. Most CA-MRSA infections are not invasive; however, fatal outcomes have been reported among healthy people with CA-MRSA invasive infections. Epidemiological studies have attributed a major burden of CA-MRSA infections in the United States to the predominant clone USA300. We investigated the association between USA300 invasive infections and mortality by conducting a systematic review and meta-analysis of studies that reported mortality rates associated with USA300 strains., Methods: We searched PubMed, bibliographies of other publications, and gray literature between January 2001 and December 2013. Observational studies of patients with an invasive MRSA infection were included. The exposure of interest was presence of USA300 invasive infection. Studies were included only if they provided MRSA PFGE types and if corresponding mortality data were the measured outcome. We pooled crude odds ratios (cORs) using a random-effects model. Woolf test of homogeneity and Q and I(2) statistics were assessed., Results: Of 574 articles identified by the search strategy, 8 met the inclusion criteria. Risk of mortality was significantly lower among patients with USA300 MRSA infections (pooled cOR, 0.63 [95% confidence interval (CI)], 0.49-0.81). There was a moderate degree of heterogeneity among study results (P = .29; I(2) = 18%). Results were observed to be heterogeneous due to study design, quality of studies, and definition of mortality., Conclusions: MRSA invasive infection with USA300 does not appear to be associated with higher mortality compared with infections due to non-USA300 strains. Nevertheless, larger well-designed studies are warranted to further evaluate this association.

We found that the selective stimulation of the intracellular, transmembrane G protein-coupled estrogen receptor (GPER), also known as GPR30, acutely lowers blood pressure after infusion in normotensive rats and dilates both rodent and human arterial blood vessels. Stimulation of GPER blocks vasoconstrictor-induced changes in intracellular calcium concentrations and vascular tone, as well as serum-stimulated cell proliferation of human vascular smooth muscle cells. Deletion of the GPER gene in mice abrogates vascular effects of GPER activation and is associated with visceral obesity. These findings suggest novel roles for GPER in protecting from cardiovascular disease and obesity.

Near-field optics uniquely addresses problems of x, y and z resolution by spatially confining the effect of a light source to nanometric domains. The problems in using far-field optics (conventional optical imaging through a lens) to achieve nanometric spatial resolution are formidable. Near-field optics serves a bridging role in biology between optical imaging and scanned probe microscopy. The integration of near-field and scanned probe imaging with far-field optics thus holds promise for solving the so-called inverse problem of optical imaging.

In a rat model of traumatic brain injury cell activation was characterized immunohistochemically from 2 h up to 2 weeks. Reactive astrocytosis became apparent perivascularly and in the grey matter within 4h after trauma. Increased OX42 immunoreactivity indicated microglial activation in cortex and hippocampus as early as 4 h, whereas up-regulation of MHC class II (OX6) was evident in white matter tracts at 24 h. Although macrophage (ED1) numbers increased in the meninges and perivascularly, brain infiltration appeared marginal. Accumulation of lymphocytes and granulocytes was not observed. Our results show that traumatic axonal injury induces a rapid and sustained glial activation in the absence of leukocyte infiltration. Thus, cell activation following diffuse trauma strongly differs from that found after focal brain damage, awaiting further functional characterization.

The loss of behaviors that organisms use to avoid predation may serve as a sensitive indicator of pollution. We tested the hypothesis that a correlation exists in the field between heavy metal levels and antipredator behaviors. We examined the antipredator behavior of aquatic caddisfly larvae and snails at sites in the Coeur d'Alene basin of Northern Idaho which varied in their levels of heavy metals. We tested the antipredator response of Physella columbiana snails at 10 polluted lakes downstream from the Bunker Hill Environmental Protection Agency (EPA) Superfund cleanup site. We then compared their behavior to snails at 14 reference lakes. We placed the snails in a plastic testing apparatus, exposed them to an extract of crushed snail, and then monitored their movements to a normally preferred shaded area. We also tested the behavior of caddisfly larvae from 36 sites from a total of 6 streams/rivers adjacent to the Superfund site. Sites were located upstream and downstream of abandoned mines. We located active larvae of four genera, simulated predation by grasping the animals between thumb and forefinger (the larvae respond to being grasped by withdrawing into their case), lifted them from the water for 3 s, and then placed them in an adjacent, slower section of the stream. We then recorded how long it took each larvae to partially emerge from its case and attempt to move away. Unlike reference site snails, snails from heavy metal-polluted environments failed to exhibit antipredator behaviors in response to crushed conspecifics. These results are consistent with previous laboratory studies. We found no effect of heavy metals on the antipredatory behavior of caddisfly larvae.

A profound inflammatory response is initiated immediately following traumatic brain injury (TBI) and is characterized by the release of several cytokines with pro- and anti-inflammatory functions. In order to elucidate which cytokines are released in the human brain in response to injury as well as in the peripheral compartment, IL-1, IL-6, IL-8, IL-10, TNF-alpha and TGF-beta were monitored in CSF and serum of severely brain-injured patients. Furthermore, we investigated the possible modulation of systemic reactions by IL-6 and the ability of IL-6 and IL-8 to promote the synthesis of nerve growth factor.

A comparison of L-valine and D-glucose transport was carried out with vesicles of plasma membrane isolated either from the luminal (brush border) or from the contra-luminal (basolateral) region of small intestinal epithelial cells. The existence of transport systems for both non-electrolytes was demonstrated by stereospecificity and saturability of uptake, as well as tracer coupling. Transport of L-valine and D-glucose differs markedly in the two types of plasma membrane with respect to stimulation by Na+. The presence of Na+ stimulated initial L-valine and D-glucose uptake in brush border, but not in basolateral membrane. Moreover, an electro-chemical Na+ gradient, oriented with the lower potential on the inside, supported accumulation of the non-electrolytes above medium concentration only in the brush border membrane. L-Valine and D-glucose transport also were saturated at lower concentrations in brush border (10-20 mM) than in basolateral plasma membranes (30-50 mM). A third difference between the two membranes was found in the effectiveness of known inhibitors of D-glucose transport. In brush border membranes phlorizin was more potent than phloretin and 2', 3', 4'-trihydroxy-4-methoxy chalcone and cytochalasin B did not inhibit at all. In contrast, with the basolateral plasma membranes the order of potency was changed to phloretin = 2',3',4'-trihydroxy-4-methoxy chalcone greater than cytochalasin B greater than phlorizin. These results indicate the presence of different types of transport systems for monosaccharides and neutral amino acids in the luminal and contra-luminal region of the plasma membrane. Active transepithelial transport can be explained on the basis of the different properties of the non-electrolyte transport systems in the two cellular regions and an electro-chemical Na+ gradient that is dependent on cellular metabolism.

The subcellular distribution of adenyl cyclase was investigated in small intestinal epithelial cells. Enterocytes were isolated, disrupted and the resulting membranes fractionated by differential and sucrose gradient centrifugation. Separation of luminal (brush border) and contra-luminal (basolateral) plasma membrane was achieved on a discontinuous sucrose gradient. The activity of adenyl cyclase was followed during fractionation in relation to other enzymes, notably those considered as markers for luminal and contraluminal plasma membrane. The luminal membrane was identified by the membrane-bound enzymes sucrase and alkaline phosphatase and the basolateral region by (Na+ + K+)-ATPase. Enrichment of the former two enzymes in purified luminal plasma membrane was 8-fold over cells and that of (Na+ + K+)-ATPase in purified bisolateral plasma membranes was 13-fold. F--activated adenyl cyclase co-purified with (Na+ + K+)-ATPase, suggesting a common localization on the plasma membrane. The distribution of K+-stimulated phosphatase and 5'-nucleotidase also followed (Na+ + K+)-ATPase during fractionation.

Changes in the oxygen partial pressure of air over the range of 8 to 258 mm of Hg did not adversely affect the photosynthetic capacity of Chlorella pyrenoidosa. Gas exchange and growth measurements remained constant for 3-week periods and were similar to air controls (oxygen pressure of 160 mm of Hg). Oxygen partial pressures of 532 and 745 mm of Hg had an adverse effect on algal metabolism. Carbon dioxide consumption was 24% lower in the gas mixture containing oxygen at a pressure 532 mm of Hg than in the air control, and the growth rate was slightly reduced. Oxygen at a partial pressure of 745 mm of Hg decreased the photosynthetic rate 39% and the growth rate 37% over the corresponding rates in air. The lowered metabolic rates remained constant during 14 days of measurements, and the effect was reversible after this time. Substitution of helium or argon for the nitrogen in air had no effect on oxygen production, carbon dioxide consumption, or growth rate for 3-week periods. All measurements were made at a total pressure of 760 mm of Hg, and all gas mixtures were enriched with 2% carbon dioxide. Thus, the physiological functioning and reliability of a photosynthetic gas exchanger should not be adversely affected by: (i) oxygen partial pressures ranging from 8 to 258 mm of Hg; (ii) the use of pure oxygen at reduced total pressure (155 to 258 mm of Hg) unless pressure per se affects photosynthesis, or (iii) the inclusion of helium or argon in the gas environment (up to a partial pressure of 595 mm of Hg).

A single culture of Chlorella pyrenoidosa (700 ml) was grown continuously under uniform environmental conditions for a period of 11 months. During this time, the culture remained uncontaminated and its oxygen production, carbon dioxide consumption, and photosynthetic quotient (PQ = CO(2)/O(2)) were monitored on a 24-hr basis. The gas exchange characteristics of the alga were found to be extremely reliable; the average oxygen production was 1.21 +/- 0.03 ml per min, the carbon dioxide consumption was 1.09 +/- 0.03 ml per min, and the PQ was 0.90 +/- 0.01 when changes in both lamp intensity and instrument accuracy were taken into consideration. Such long-term dependability in the production of oxygen, consumption of carbon dioxide, and maintenance of a uniform PQ warrants the use of C. pyrenoidosa in a regenerative life support system for space travel.

The oxygen production of a photosynthetic gas exchanger containing Chlorella pyrenoidosa (1% packed cell volume) was measured when various concentrations of carbon dioxide were present within the culture unit. The internal carbon dioxide concentrations were obtained by manipulating the entrance gas concentration and the flow rate. Carbon dioxide percentages were monitored by means of electrodes placed directly in the nutrient medium. The concentration of carbon dioxide in the nutrient medium which produced maximal photosynthesis was in the range of 1.5 to 2.5% by volume. Results were unaffected by either the level of carbon dioxide in the entrance gas or the rate of gas flow. Entrance gases containing 2% carbon dioxide flowing at 320 ml/min, 3% carbon dioxide at 135 ml/min, and 4% carbon dioxide at 55 ml/min yielded optimal carbon dioxide concentrations in the particular unit studied. By using carbon dioxide electrodes implanted directly in the gas exchanger to optimize the carbon dioxide concentration throughout the culture medium, it should be possible to design more efficient large-scale units.

Continuously growing cultures of Chlorella pyrenoidosa Starr 252, operating at constant density and under constant environmental conditions, produced uniform photosynthetic quotient (PQ = CO(2)/O(2)) and O(2) values during 6 months of observations. The PQ for the entire study was 0.90 +/- 0.024. The PQ remained constant over a threefold light-intensity change and a threefold change in O(2) production (0.90 +/- 0.019). At low light intensities, when the rate of respiration approached the rate of photosynthesis, the PQ became extremely variable. Six lamps of widely different spectral-energy distribution produced no significant change in the PQ (0.90 +/- 0.025). Oxygen production was directly related to the number of quanta available, irrespective of spectral-energy distribution. Such dependability in producing uniform PQ and O(2) values warrants a consideration of algae to maintain a constant gas environment for submarine or spaceship use.

The bacterium Hydrogenomonas eutropha is under consideration for use in a regenerative life-support system for manned space missions of long duration. A 4-liter continuous culture unit containing the organism was operated for a period of 272 days under autotrophic environmental conditions. The best steady-state run achieved with this unit was observed over a 22-day time interval after 181 days of operation. During this time, the culture consumed an average of 22.9 +/- 2.0 ml of carbon dioxide per min, 38.1 +/- 3.3 ml of oxygen per min, and 128.5 +/- 10.6 ml of hydrogen per min. It required 18.7 +/- 1.2 liters of fresh nutrient medium per 24 hr to maintain a constant, preestablished cell population of 1.65 g (dry weight) per liter. The ratio of consumption of carbon dioxide, oxygen, and hydrogen varied from 1:1.2:4.5 to 1:1.9:6.6, with an average of 1:1.7:5.7. Based on these values, approximately 60 liters of the culture would be necessary to balance the gas exchange of one man.